1-((3-Methoxyphenyl)sulfonyl)piperidine: Piperidine, 1-[(3-methoxyphenyl)sulfonyl]-

compd 1
3-Methoxy-N-morpholinobenzenesulfonamide: Benzenesulfonamide, 3-methoxy-N-4-morpholinyl-; (1) (1255365-27-5)

¹H NMR pdf(400 MHz, CDCl₃, 7.27 ppm) δ: 2.64 (t, J = 4.8 Hz, 4 H (NCH₂CH₂O)₂), 3.62 (t, J = 4.8 Hz, 4 H, (NCH₂CH₂O)₂), 3.87 (s, 3 H, OMe), 5.60 (s, 1 H, NH), 7.14 (dd, J = 8.0, 2.0 Hz, 1 H, Ar-H), 7.43 (t, J = 8.0 Hz, 1 H, Ar-H), 7.49 (t, J = 2.0 Hz, 1 H, Ar-H), 7.57 (d,J = 8.0 Hz, 1 H, Ar-H); ¹³C NMR pdf(100 MHz, CDCl₃, 77.0 ppm) δ: 55.6, 56.4, 66.5, 112.5, 119.4, 120.1, 129.8, 139.7, 159.6; IR n _max (film)/cm^-1 3212, 2963, 2856, 1597, 1478, 1433, 1361, 1317, 1287, 1242, 1157, 1109, 1034, 864, 685 (principal peaks); HRMS (FTMS+ p-NSI) found m/z 295.0721 [M+Na]⁺, C₁₁H₁₆N₂O₄SNa requires m/z 295.0723. Reverse phase HPLC analysis reveals purity >99% (run on an Agilent Zorbax SB-C18, 5 µm, 4.6 x 150 mm column (23 °C) at a flow rate of 1.5 mL/min of 70:30 MeCN:H₂O observed at 210 nm giving a retention time of 1.32 min, 1.0 mg/mL in CH₃CN).


compd 2

1-((3-Methoxyphenyl)sulfonyl)piperidine: Piperidine, 1-[(3-methoxyphenyl)sulfonyl]-; (2) (173681-65-7)
mp 115-116 °C;


 ¹H NMR pdf(400 MHz, DMSO-d₆, 2.50 ppm) 
δ: 1.30-1.35 (m, 2 H, N(CH₂CH₂)₂CH₂), 
1.47-1.52 (m, 4 H, N(CH₂CH₂)₂CH₂),
2.85 (t, J = 5.2 Hz, 4 H, N(CH₂CH₂)₂CH₂), 
3.83 (s, 3 H, OMe), 
7.16 (t, J = 2.1 Hz, 1 H, Ar-H), 
7.25-7.30 (m, 2 H, Ar-H), 
7.55 (t, J = 8.0 Hz, 1 H, Ar-H);





 ¹³C NMRpdf(100 MHz, DMSO-d₆, 39.5 ppm) δ: 22.8, 24.7, 46.6, 55.6, 112.3, 118.7, 119.5, 130.5, 136.7, 159.5; 


IR n_max(film)/cm^-1 2940, 2851, 1597, 1478, 1359, 1340, 1318, 1287, 1241, 1167, 1098, 1040, 931, 856, 724, 688; (principal peaks); 


HRMS (FTMS+p-NSF) found m/z 256.1002 [M+H]⁺, C₁₂H₁₈ NO₃S requires m/z 256.1002. 

Reverse phase HPLC analysis reveals purity >99% (run on an Agilent Zorbax SB-C18, 5 µm, 4.6 x 150 mm column (23 °C) at a flow rate of 1.5 mL/min of 75:25 MeCN:H₂O observed at 210 nm giving a retention time of 1.95 min, 1.0 mg/mL in MeCN).

1,3-Dimethyl-3-(p-tolyl)-1H-pyrrolo[3,2-c]pyridin-2(3H)-one

1,3-Dimethyl-3-(p-tolyl)-1H-pyrrolo[3,2-c]pyridin-2(3H)-one

3: ¹H NMR pdf(500 MHz, CDCl₃)

δ: 1.80 (s, 3 H), 2.29 (s, 3 H), 3.21 (s, 3 H), 
6.88 (d, J = 5.5 Hz, 1 H), 7.12 (d, J = 8.0 Hz, 2 H), 7.21-7.19 (m, 2 H), 8.35 (s, 1 H), 8.52 (d, J = 5.0 Hz, 1 H); 

¹³C NMR pdf(125 MHz, CDCl₃) δ: 20.7, 23.7, 26.2, 50.3, 103.8, 126.1, 129.2, 130.1, 136.4, 137.2, 144.3, 149.7, 150.2, 179.0; 


IR (cast, cm^-1): 3028, 2972, 2931, 1728, 1603, 1512, 1496, 1373, 1338, 1110, 1018, 818; 


HRMS (ESI): calcd. for C₁₆H₁₇N₂O ([M+H]⁺): 253.1335, found: 253.1333; mp 103-104 °C; 

Anal. calcd. for C₁₆H₁₆N₂O: C, 76.16; H, 6.39; N, 11.10, found: C, 76.09; H, 6.39; N, 11.11.








also

Analytical data for 2:

 ¹H NMR pdf(500 MHz, CDCl₃) δ: 1.40 (d, J = 7.0 Hz, 3 H), 2.30 (s, 3 H), 3.25 (s, 3 H), 3.71 (q, J = 6.5 Hz, 1 H), 6.95 (d, J = 7.5 Hz, 2 H), 7.00 (br d, J = 5.4 Hz, 2 H), 7.05 (d, J = 8.0 Hz, 2 H), 8.57-8.58 (m, 2 H); 

¹³C NMR pdf(125 MHz, CDCl₃) δ: 20.4, 20.8, 36.9, 43.1, 121.5, 126.9, 129.2, 136.3, 138.0, 150.9, 151.0, 173.3; 

IR (cast, cm^-1): 2975, 2930, 1668, 1587, 1513, 1496, 1375, 1274, 1126, 1063, 1024, 826; 

HRMS (ESI): calcd. for C₁₆H₁₉N ₂O ([M+H]⁺): 255.1492, found: 255.1488; mp 91-92 °C; 

Anal. calcd. for C₁₆H₁₈N₂O: C, 75.56; H, 7.13; N, 11.01, found: C, 75.47; H, 7.21; N, 11.

α-Chloro-[2-(ethoxycarbonyl)-3-methoxy]benzeneacetic acid, Ethyl ester

Procedure for the Insertion into α-Chloromalonate 4a

To a suspension of CsF (183 mg, 1.2 mmol) in MeCN (2.0 mL) were added diethyl α-chloromalonate (4a, 32 µL, 0.20 mmol) and 3-methoxy-2-(trimethylsilyl)phenyl triflate (1, 63 µL, 0.24 mmol) under argon atmosphere at −20 °C. After being stirred at −20 °C to room temperature for 12 h, the reaction mixture was diluted with saturated NaHCO3 and then extracted with AcOEt. The organic phase was dried over Na2SO4 and concentrated at reduced pressure. Purification of the residue by PTLC (AcOEt/hexane =1:2) afforded the product 9 (31 mg, 52%).

α-Chloro-[2-(ethoxycarbonyl)-3-methoxy]benzeneacetic acid, Ethyl ester (9). 

IR (KBr) 2983, 1752, 1736, 1589, 1472, 1442 cm−1. 

1H-NMR (CDCl3) δ 7.40 (1H, t, J = 8.2 Hz), 7.25 (1H, br d, J = 8.5 Hz), 6.93 (1H, br d, J = 8.5 Hz), 5.50 (1H, s), 4.42 (2H, q, J = 7.1 Hz), 4.27–4.15 (2H, m), 3.83 (3H, s), 1.39 (3H, t, J= 7.1 Hz), 1.24 (3H, t, J = 7.1 Hz). 

13C-NMR (CDCl3) δ 167.8, 166.5, 156.6, 134.6, 131.2, 123.2, 120.4, 111.9, 62.6, 61.7, 56.1, 55.6, 14.1, 13.9. 

HRMS (ESI+) calcd for C14H1735ClO5Na (M+Na+): 323.0657, Found: 323.0642; HRMS (ESI+)calcd for C14H1737ClO5Na (M+Na+): 325.0633, Found: 325.0613.

4-Methoxy-2-benzofurancarboxylic acid, Ethyl ester

4-Methoxy-2-benzofurancarboxylic acid, Ethyl ester

Procedure for the Synthesis of Benzofuran 15a

To a suspension of CsF (304 mg, 2.0 mmol) in DMF (4.0 mL) were added 3-methoxy-2-(trimethylsilyl)phenyl triflate (1, 105 µL, 0.40 mmol) and ethyl iodoacetate 14 (95 µL, 0.80 mmol) under argon atmosphere at 100 °C. After being stirred at the same temperature for 12 h, the reaction mixture was diluted with saturated NaHCO3 and then extracted with CH2Cl2. The organic phase was dried over Na2SO4 and concentrated at reduced pressure. Purification of the residue by flash silica gel column chromatography (EtOAc/hexane = 1:20–1:4) afforded the product 15a (35 mg, 40%). Product 16 was also formed.

4-Methoxy-2-benzofurancarboxylic acid, Ethyl ester (15a). Colorless oil. 

IR (KBr) 2981, 1726, 1609, 1570, 1500 cm−1. 

1H-NMR (CDCl3) δ 7.62 (1H, d, J = 1.0 Hz), 7.35 (1H, t, J = 8.2 Hz), 7.18 (1H, d, J = 8.2 Hz), 6.67 (1H, d, J = 8.2 Hz), 4.43 (2H, q, J = 7.1 Hz), 3.94 (3H, s), 1.41 (3H, t, J = 7.1 Hz). 

13C-NMR (CDCl3) δ 159.5, 156.9, 154.6, 144.4, 128.5, 117.8, 111.6, 105.1, 103.5, 61.4, 55.6, 14.3. 

HRMS (ESI+) calcd for C12H13O4 (M+H+): 221.0808, Found: 221.0806.

Procedure for Transformation of Dihydrobenzofuran 8a into Benzofuran 15a

To a solution of dihydrobenzofuran 8a (50 mg, 0.16 mmol) in THF (3.2 mL) was added KHMDS (0.50 M in toluene, 320 µL, 0.16 mmol) under argon atmosphere at −40 °C. After being stirred at the same temperature for 12 h, the reaction mixture was diluted with saturated NaHCO3 and then extracted with CH2Cl2. The organic phase was dried over Na2SO4 and concentrated at reduced pressure. Purification of the residue by PTLC (EtOAc/hexane = 1:4 with 2% CH2Cl2) afforded benzofuran 15a (33 mg, 96%).
http://www.mdpi.com/1420-3049/19/1/863/htm

5-Chloro-3-ethoxycarbonylbenzofuran.

3-Benzofurancarboxylic acid, 5-chloro-, ethyl ester; (899795-65-4)


Physical and spectroscopic properties of 5-chloro-3-ethoxycarbonylbenzofuran are as follows: 
mp 60.5-61.5 °C; 

¹H NMR pdf (CDCl₃, 400 MHz) δ: 1.43 (t, J = 7.2 Hz, 3 H), 4.42 (q, J = 7.2 Hz, 2 H), 7.32 (dd, J = 2.1, 8.8 Hz, 1 H), 7.44 (d, J = 8.8 Hz, 1 H), 8.03 (d, J = 2.1 Hz, 1 H), 8.26 (s, 1 H); 


¹³C NMR pdf (CDCl₃, 100 MHz) δ: 14.4, 60.8, 112.7, 114.6, 121.8, 125.6, 126.0, 130.0, 152.0, 153.9, 162.9; 

HRMS (EI) m/z calcd for C₁₁H₉O₃Cl: 224.02407; found: 224.0241. 

Anal. Calcd for C₁₁H₉O₃Cl: C, 58.82; H, 4.04. Found: C, 58.54; H, 4.01.

(+)-(3aS,7aR)-Hexahydro-(3S,6R)-dimethyl-2(3H)-benzofuranone

(3aS,7aR)-HEXAHYDRO-(3S,6R)-DIMETHYL-2(3H)-BENZOFURANONE, 
3aS,7aR-hexahydro-3S,6R-dimethyl-2(3H)-benzofuranone, 
(+)-(3aS,7aR)-Hexahydro-(3S,6R)-dimethyl-2(3H)-benzofuranone (79726-51-5)

The lactone is identical to that previously reported⁴ and has the following spectral data: IR (neat) cm⁻¹: 1770, 1453, 1375, 1290, 1190, 1096, 847; 

¹H NMR (360 MHz, CDCl₃) δ: 0.99–1.38 (m, 3 H), 1.02 (d, 3 H, J = 6.5), 1.15 (d, 3 H, J = 7.6), 1.59 (m, 1 H), 1.78 (m, 2 H), 1.92 (m, 1 H), 2.25 (m, 1 H), 2.64 (quint., 1 H, J = 7.6), 4.00 (dt, 1 H, J = 11, 4); 

¹³C NMR (360 MHz, CDCl₃) δ: 9.57, 21.99, 23.77, 31.25, 34.15, 38.72 (2 carbons), 47.09, 81.38, 180.27. It has [α]_D20 +106.2° (CHCl₃, c 0.6). 

The checkers recorded [α]_D25 of +72 to +88° (CHCl₃, c 0.6). If the temperature of the distillation exceeds 110°C, a decrease in [α]_D might be observed because of epimerization α to the lactone carbonyl. If the pure diastereomer is required, it is recommended that purification be effected by column chromatography over silica gel (eluent, pentane:ethyl acetate 20:1). Typically, the lactone is obtained in a yield of55% with an [α]_D20 +149° (CHCl₃, c 1.1).

ref 4

1. Jefford, C. W.; Wang, Y. J. Chem. Soc., Chem. Commun. 1988, 634.