(3,4-DICHLORO-PHENYL)-ACETIC ACID METHYL ESTER

6725-44-6

Methyl 3,4-dichlorophenylacetate

(3,4-DICHLORO-PHENYL)-ACETIC ACID METHYL ESTER
Clc1ccc(cc1Cl)CC(=O)OC
sandeep@ubcforums.com

Institute for Chemical Research
Gokasho Uji-city, Kyoto

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(3,4,5,6-tetrahydro-lH-thieno[3,4-c]pyrrole 2,2- dioxide hydrobromide

(3,4,5,6-tetrahydro-lH-thieno[3,4-c]pyrrole 2,2- dioxide hydrobromide; (2b)
 


Synthesis of substituent R² (3,4,5,6-tetrahydro-lH-thieno[3,4-c]pyrrole 2,2- dioxide hydrobromide; (2b) was carried out as shown in Scheme-4 and the stepwise procedure is depicted below:
Scheme-4:

Bz-NH

Substitued R² (2b)
Step-1 : 2,3-dimethylbuta-L3-diene (14)
To 2,3-dimethylbutane-2,3-diol (13, 85g), 48% aqueous HBr was added to get the colorless solution. Mixture was fractionally distilled, washed twice with water and dried over anhydrous CaCl₂. Mixture was redistilled and the fraction of 69-70 °C was collected to get 2,3-dimethylbuta-l,3-diene (14, 38g. 64%yield). 1H NMR: (CDCl₃, 400 MHz): δ 5.06 (2H, s), 4.97 (2H, s), 1.92 (6H, s); ESI-MS: (+ve mode) 83.3 (M+H)⁺ (70 %).


Step-2: 3,4-dimethyl-2,5-dihydrothiophene 1,1 -dioxide (15)
A mixture of hydroquinone (492mg) and 2,3-dimethylbuta-l ,3-diene (14, 31.96 ml) was placed in sealed tube and a solution of sulfur dioxide in MeOH (140 ml) was added. Reaction mixture was heated at 85 °C for 4 h and cooled to room temperature. Crystals obtained was filtered, washed with cold methanol and dried to get 3,4- dimethyl-2,5-dihydrothiophene 1,1 -dioxide (15) as white crystalline solid (30 gm, 72% yield).
lH NMR: (CDCl_3, 400 MHz): δ 3.73 (4H, d, J = 1.2 Hz), 1.78 (6H, t, J = 1.2 Hz); ESI- MS: (+ve mode) 147.2 (M+H)⁺ (70 %), 169.1 (M+Na)⁺ (40%).


Step-3: 3,4-bis(bromomethyl)-2,5-dihydrothiophene 1,1 -dioxide (16)
A mixture of 3,4-dimethyl-2,5-dihydrothiophene 1,1-dioxide (15, 20g), 1- bromopyrrolidine-2,5-dione (53.5g), and AIBN (400mg) in CHC1₃ was heated for 15 hr. After completion of reaction, filtrate was evaporated under reduced pressure. The residue obtained was recrystallize from methanol to get 3,4-bis(bromomethyl)-2,5- dihydrothiophene 1,1-dioxide as a white crystals (16, 19 g, 45% yield).
1H NMR: (CDC1_3> 400 MHz): δ 4.06 (4H, s), 4.01 (4H, s); ESI-MS: (+ve mode) 303.8 (M+H)⁺ (90 %), 305.7 (M+2H)⁺ (70%).


Step-4: 5-benzyl-3,4,5,6-tetrahydro-lH-thieno[3,4-c]pyrrole 2,2-dioxide (17)
Mixture of 3,4-bis(bromomethyl)-2,5-dihydrothiophene 1,1-dioxide (16, 12g) and phenylmethanamine (10.84ml) in acetonitrile was stirred at 25 °C for 2 hr. After completion of reaction, solvent was removed under reduced pressure, ethyl acetate and IN NaOH were added, organic layer was separated and aq layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to give 5-benzyI-3,4,5,6-tetrahydro- lH-thieno[3,4-c]pyrrole 2,2-dioxide (17) as a solid compound (3.7 g, 38% yield).
1H NMR: (CDCI_3, 400 MHz): δ 7.34-7.29 (5H, m), 3.88 (2H, s), 3.77 (4H,s), 3.61 (4H, s); ESI-MS: (+ve mode) 250.3 (M+H)⁺ (100 %).

Step-5: benzyl 4,6-dihvdro-lH-thieno[3,4-clpyrrole-5(3H^")-carboxylate 2,2-dioxide (IS) A mixture of 5-benzyl-3,4,5,6-tetrahydro-lH-thieno[3,4-c]pyrrole 2,2-dioxide (17, 3.6g) and CBZ-C1 (13.5 ml) in toluene was stirred for 3 hr. After completion of reaction, diethyl ether was added till solid precipitated out. Solid was filtered and dried under reduced pressure to get benzyl 4,6-dihydro-lH-thieno[3,4-c]pyrrole-5(3H)- carboxylate 2,2-dioxide (18, 2.7 g, 64% yield). ^lH NMR: (CDC1_3, 400 MHz): δ 7.38-7.35 (5H, m), 5.19 (2H, s), 4.31 (4H, s), 3.88 (4H, d, J = 13.6 Hz); ESI-MS: (+ve mode) 294.4 (M+H)⁺ (80 %).


Step-6: 3 A5,6-tetrahydro-lH-thieno[3,4-c]pyrrole 2,2-dioxide hydrobromide (2b)
To a solution of benzyl 4,6-dihydro-lH-thieno[3,4-c]pyrrole-5(3H)-carboxylate 2,2-dioxide (18, 3.7 g) in glacial acetic acid, HBr in glacial acetic acid was added and the reaction mixture was stirred at 2 °C for 3h. After completion of reaction, diethyl ether was added to afford sticky solid, solvent was decanted and added minimum amount of methanol to get the crystalline solid as 3,4,5,6-tetrahydro-lH-thieno[3,4- c]pyrrole 2,2-dioxide hydrobromide as a hydrobromide salt (2b, 1.5 g, 50% yield). 1H NMR: (CDCI₃, 400 MHz): δ 9.43 (2H, bs), 4.08 (4H, s), 4.02 (4H, s); ESI-MS: (+ve mode) 160.4 (M+H)⁺ (88 %).


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