Aluminium lithium hydride → ((3R,4S)-1-Benzyl-4-phenylpyrrolidin-3-YL)methanol
Reaction equation
[CH2:1]([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C@@H:10]([C:19](N2[C@@H](CC3C=CC=CC=3)COC2=O)=[O:20])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH2:1]([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C@@H:10]([CH2:19][OH:20])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1Participants
Procedure
A solution of 3-(1-benzyl-4-(S)-phenylpyrrolidine-3-(R)-carbonyl)-4-(S)-benzyl oxazolidin-2-one (from Step B) in 2.5 L of THF at 10° C. was treated with 1.18 L of 1.0 M lithium aluminum hydride solution in THF over a period of 2 h. The resulting mixture was warmed to rt and stirred for 20 h. The reaction was quenched by adding 40 mL of H2O, then 40 mL of 2.0 N NaOH, then 115 mL of H2O and then was stirred at rt for 1.5 h. The mixture was filtered and the filtrate was concentrated. Chromatography on 4 kg of silica using 4:1 hexanes/acetone (14 L), then 7:3 hexanes/acetone as the eluant to afford the title compound: 1H NMR (400 MHz) δ 2.38–2.46 (m, 2H), 2.78–2.88 (3H), 3.20–3.26 (2H), 3.65 (dd, J=12.0, 4.0, 1H), 3.66 (app s, 2H), 3.74 (dd, J=12.0, 4.0, 1H), 7.18–7.34 (10H); ESI-MS 268 (M+H); HPLC A: 2.35 min.
Workup
- customThe reaction was quenched
- additionby adding 40 mL of H2O
- stirring40 mL of 2.0 N NaOH, then 115 mL of H2O and then was stirred at rt for 1.5 h
- filtrationThe mixture was filtered
- concentrationthe filtrate was concentrated
Sources & evidence
- ORD record
- ord-7892614a79e248b79aa0a72e28d011b7
- Source dataset
- uspto-grants-2006_10
- Patent number
- US07125887B2
Reaction notes
Loading…