1-[(2S)-1-HYDROXY-2-BUTANYL]-2-PYRROLIDINONE......LEVETIRACETAM INTERMEDIATE

• 1-[(2S)-1-HYDROXY-2-BUTANYL]-2-PYRROLIDINONE     
• CAS No.: 909566-58-1
• Formula: C8H15NO2
• Molecular Weight: 157.21000

1H NMR PREDICT




13 C NMR PREDICT

PATENT

ROUTE FROM D-(+)-2-amino butanol 

http://www.google.im/patents/WO2006095362A1?cl=en

WO 2006/095362 

WO 2006/095362 describes a process for the preparation of levetiracetam, which is summarized in scheme 3:

 Thus according to one aspect the present invention relates to a process for the preparation of (S)-(-)-α~ethyl-2-oxo-l-pyrrolidineacetamide of Formula (I), comprising the steps of :

i) condensation of (S)-2-amino butanol of Formula (IΙ)and 4-halobutryl chloride, where halo group can be chloro, bromo or iodo in solvents to form α-ethyl-2-oxo pyrrolidine ethanol of Formula (III)

................(H) ...........................................................................(III)

Preparation of (S)-α-ethyl-2-oxo pyrrolidine ethanol (III) 

184 g of anhydrous Na₂SO₄ is added to a suspension of 100 g (1.123 mole) of (S)-2- amino butanol in 800ml of Toluene at ambient temperature. The mixture is cooled to 0 to 5°C. Then, 188 g of powder potassium hydroxide is added to the mixture followed by the addition of 173.4 g of 4-chlorobutyryl chloride in 100 ml of Toluene drop wise at 0⁰C , with vigorous stirring . Ten hrs later, the reaction mixture is filtered over Hyflo-cel and the filtrate evaporated under reduced pressure . The crude product is purified by high vacuum distillation ( 137-14O⁰C at 2 mm pressure). Yield : 167.8 g ( 95%) [oc]²⁵= -27.46 (C=I, acetone)

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

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(2S)-2- Oxopyrrolidin-1-yl)butanoic acid.............Key Levetiracetam intermediate

(s)-2-(2-oxopyrrolidin-1-yl)butanoic Acid
CAS No.:	102849-49-0
Synonyms:	(2S)-2-(2-Oxopyrrolidin-1-yl)butanoic acid;
Formula:	C8H13NO3
Exact Mass:	171.09000

 MP 124⁰C ; [oc]²⁵= -24.32 (c=l, acetone)........WO2006095362
Mp: 124–125 °C; [α] 25 D = – 24.3 (c l.0, acetone);Journal of Chemical and Pharmaceutical Research, 2012, 4(12):4988-4994



1H NMR PREDICT

 1H NMR (CDCl3, 400 MHz): δ 0.93 (t, J = 7.7 Hz, 3H), 1.67–1.76 (m, 1H), 1.99–2.13 (m, 3H), 2.49 (t, J = 7.7 Hz, 2H), 3.37 (m, J = 8.7, 5.8 Hz, 1H), 3.52-3.58 (m, 1H), 4.64 (dd, J = 10.6, 4.8 Hz, 1H);
Journal of Chemical and Pharmaceutical Research, 2012, 4(12):4988-4994

13 C NMR PREDICT

13C NMR (CDCl3, 125 MHz) : δ 10.8, 18.2, 21.9, 30.8, 43.9, 55.4, 173.7, 177.2;
Journal of Chemical and Pharmaceutical Research, 2012, 4(12):4988-4994 

Cosy predict.BELOW

SYNTHESIS AS IN PAPER

Asymmetric synthesis of chiral amines by highly diastereoselective 1,2-additions of organometallic reagents to N-tert-Butanesulfinyl Imines

 Chandra Babu K1,2*, Buchi Reddy R3 , Mukkanti K2 , Madhusudhan G1 and Srinivasulu P1
1 Inogent Laboratories (A GVK BIO Company), 28A, IDA, Nacharam, Hyderabad 500 076, India 2Centre for Pharmaceutical Sciences, JNT University, Kukatpally, Hyderabad 500 072, India
3Orchid Chemicals & Pharmaceuticals Ltd, 476/14, R&D Centre, Chennai -600 119, India __________________________________________________________________________
http://jocpr.com/vol4-iss12-2012/JCPR-2012-4-12-4988-4994.pdf


ABSTRACT We report an asymmetric synthesis of chiral amines (4S,5S)-Cytoxazone, Taxol side chain moiety and (S)- Levetiracetam starting from versatile new chiral N- sulfinimine (4). The key step, stereoselective 1,2-addition of Grignard reagent to chiral N-sulfinimine derived from (R)-glyceraldehyde acetonide and (S)-t-BSA gave the corresponding sulfonamide in high diastereoselectivity. Subsequent reactions yielded the targeted biological active and pharmaceutical important compounds with high purity (>99%) and yield

Journal of Chemical and Pharmaceutical Research, 2012, 4(12):4988-4994

 (S)-2-(2-oxopyrrolidin-1-yl)butanoic acid, 16 Potassium hydroxide (1.0 g, 0.017 mol)) was dissolved into water (18.0 ml). Tetra-n-butyl ammonium bromide (0.2 g, 0.0062 mol)) and (S)-15 (1.0 g, 0.0063 mol)) in methylene chloride (10 ml) were charged in 30 min. charged Potassium permanganate (1.5 g, 0.094 mol)). After completion of reaction filtered through a celite bed and washed with water (10.0 ml). The aqueous layer pH was adjusted to 3 using hydrochloric acid (2 ml). Added sodium phosphate (2.5 g, 0.0152 mol) and toluene (25.0 ml). The reaction mixture extracted with dichloromethane (5 x 25 ml). The organic solution was dried with (Na2SO4) distilled under vacuo to give compound 16 as oil. To the residue toluene (10 ml) was added and stirred at 0 °C for about 30 min. The solid was filtered and washed with toluene (5 ml) afford the pure compound 16 (0.83g, 76%);

Mp: 124–125 °C; [α] 25 D = – 24.3 (c l.0, acetone);


1H NMR (CDCl3, 400 MHz): δ 0.93 (t, J = 7.7 Hz, 3H), 1.67–1.76 (m, 1H), 1.99–2.13 (m, 3H), 2.49 (t, J = 7.7 Hz, 2H), 3.37 (m, J = 8.7, 5.8 Hz, 1H), 3.52-3.58 (m, 1H), 4.64 (dd, J = 10.6, 4.8 Hz, 1H);

13C NMR (CDCl3, 125 MHz) : δ 10.8, 18.2, 21.9, 30.8, 43.9, 55.4, 173.7, 177.2;


IR (CHCl3) ν max : 2975, 1731, 1620 cm–1; ESI-MS: m/z 170.0 [M- +1].


'..........................

PATENT

ROUTE FROM D-(+)-2-amino butanol 

http://www.google.im/patents/WO2006095362A1?cl=en

WO 2006/095362 

Example-2 Preparation of (S)-α-ethyl-2-oxo pyrrolidine acetic acid (IV)

A mixture of 225 g of (S)-α- ethyl -2-oxo pyrrolidine ethanol and a solution of 44.8 g of sodium carbonate in 4500 ml of water placed in a 10 litre round bottomed flask. Then 340 g of potassium permanganate is added to the reaction mixture with vigorous stirring, during 3-4 hours, cooling the mixture to 0°-5°C by immersing in a bath of ice water. Allow the reaction mixture to attain room temperature gradually. 15 hours later, filter off the precipitated manganese dioxide, concentrated the filtrate to about 1000 ml under reduced pressure and acidified with dilute sulphuric acid up to pH 2 followed by the saturation with NaCl. Cover the solution with a layer of dichloromethane. Separate the dichloromethane layer and extract the aqueous layer two to three times with 100 ml portions of dichloromethane and distilled off on rotavapor. Recrystallised the crude acid (209 g) from 210 ml of toluene; filter and wash with toluene . Yield : 130 gm (54 %) ; MP 124⁰C ; [oc]²⁵= -24.32 (c=l, acetone)

Orchid Chemicals & Pharmaceuticals Ltd











Centre for Pharmaceutical Sciences, JNT University















Inogent Laboratories (A GVK BIO Company)

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

COCK WILL TEACH YOU NMR

COCK SAYS MOM CAN TEACH YOU NMR

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

http://newdrugapprovals.org/

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(S)-2-amino-butanamide hydrochloride.......... Key intermediate of Levetiracetam

(S)-2-amino-butanamide hydrochloride 

Key intermediate of Levetiracetam

• CAS Number 7682-20-4
    
 

• Linear Formula CH₃CH₂CH(NH₂)CONH₂ · HCl
   
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Stage B

(S)-2-aminobutyramide hydrochloride Preparation

Into the above (S)-2-aminobutyric acid methyl ester hydrochloride is added Isopropanol is then added, followed by the introduction of ammonia gas at a pressure about 60 psi (413 kPa) until the reaction is complete. After filtering to remove formed ammonium chloride, the solvent is partially evaporated and isopropanol hydrochloride is added. The mixture is stirred while solid product forms, then the solid is separated by filtration and washed with isopropanol.

The product was characterized by the following ¹H NMR data (200 MHz, DMSO-d₆): 0.9-1.0(t,3H), 1.8-1.9(Q,2H), 3.7-3.8(t, 1H), 7.5-7.7(Br,NH₂), 8.0-8.2(Br,NH₂)

1H NMR PREDICT

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13C NMR PREDICT

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

COCK WILL TEACH YOU NMR

COCK SAYS MOM CAN TEACH YOU NMR

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

http://newdrugapprovals.org/

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