Dimethylformamide → 5,6-Dihydro-6-hydroxy-5,5-dimethyl-7-(2-oxopyrrolidin-1-yl)-7H-thieno[3,2-b]pyran
Reaction equation
[H-].[Na+].Br[CH:4]1[C:9]([CH3:11])([CH3:10])[O:8][C:7]2[CH:12]=[CH:13][S:14][C:6]=2[CH:5]1O.[NH:16]1[CH2:20][CH2:19][CH2:18][C:17]1=[O:21].[K+].[Br-].CN(C)C=[O:27]>>[OH:27][CH:4]1[C:9]([CH3:11])([CH3:10])[O:8][C:7]2[CH:12]=[CH:13][S:14][C:6]=2[CH:5]1[N:16]1[CH2:20][CH2:19][CH2:18][C:17]1=[O:21]Participants
Procedure
Sodium hydride (60% in oil, 1.17 g, 29.3 mmol) was added to a solution of 6-bromo-7-hydroxy-5,6-dihydro-5,5-dimethyl-7H-thieno [3,2-b]pyran (7.0 g, 26.6 mmol) in N,N-dimethylformamide (115 mL) at 0° C. The resultant mixture was stirred at rt for 2 h. 2-Pyrrolidinone (6.1 mL, 79.8 mmol) was added to the solution followed by sodium hydride (60% in oil, 1.17 g, 29.3 mmol) and stirring was continued at rt for 4 days. The solution was poured into ice water (500 mL) and extracted with dichloromethane. The dichloromethane solution was washed with water (5x) and dried over sodium sulfate. The solvent was evaporated in vacuo and the resultant solid was triturated in diethyl ether to give the product, 3.91 g (55%), as a colorless solid: mp 154°-155° C.; IR (KBr): 3263, 1665 and 1562 cm- ; MS: m/z 268 (MH+); 1H NMR (CDCl3) δ 1.30 (s, 3H), 1.50 (s, 3H), 2.07 (m, 2H), 2.52 (m, 2H), 3.00 (d, J=5.5 Hz, 1H, exchanges with D2O), 3.35 (m, 2H), 3.78 (dd, J=5.5 Hz, J=9.0Hz 1H, simplifies to d, J=9.0 Hz, with D2O), 5.28 (d, J=9.0 Hz, 1H), 6.57 (d, 5.4 Hz, 1H) and 7.11 (d, J=5.4 Hz, 1H).
Workup
- extractionextracted with dichloromethane
- washThe dichloromethane solution was washed with water (5x)
- dry with materialdried over sodium sulfate
- customThe solvent was evaporated in vacuo
- customthe resultant solid was triturated in diethyl ether
- customto give the product, 3.91 g (55%)
Sources & evidence
- ORD record
- ord-1d30bf6126a9482c968d0f411fc8b5f7
- Source dataset
- uspto-grants-1994_02
- Patent number
- US05284857
Reaction notes
Loading…