Hydrochloric Acid → (S)-3-Hydroxy-1-(4-methylbenzyl)pyrrolidin-2-one
Reaction equation
Cl.[Si]([O:9][C@H:10]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[C:11]1=[O:23])(C(C)(C)C)(C)C>C(Cl)Cl>[OH:9][C@H:10]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[C:11]1=[O:23]Participants
Procedure
HCl (4 M in 1,4-dioxane, 25.5 ml, 102 mmol) was added in one portion to a solution of (S)-3-((tert-butyldimethylsilyl)oxy)-1-(4-methylbenzyl)pyrrolidin-2-one (6.53 g, 20.4 mmol) in anyhdrous DCM (20.44 ml) at rt. A slight exotherm was noted. The reaction mixture was allowed to stir at rt for 2 h and then evaporated in vacuo. The residue was taken up in DCM (100 mL) and washed with a satd. sodium bicarbonate solution (100 mL) and brine (50 mL), and then the solution was dried over MgSO4 and concentrated to a residue. The crude product was purified by silica gel chromatography (120 g of silica) eluting with a gradient of 40% to 100% ethyl acetate in hexanes to provide 3.73 g (89%) of the desired product. LC/MS (Conditions B) RT=2.338 min, (M+H)+=206.2; 1H NMR (400 MHz, chloroform-d) δ 7.26-7.02 (m, 4H), 4.43 (d, J=3.5 Hz, 2H), 4.41-4.37 (m, 1H), 3.66 (d, J=2.6 Hz, 1H), 3.34-3.05 (m, 2H), 2.41 (dddd, J=12.8, 8.4, 6.6, 2.2 Hz, 1H), 2.34 (s, 3H), 1.93 (dq, J=12.8, 8.8 Hz, 1H).
Workup
- customevaporated in vacuo
- washwashed with a satd
- dry with materialsodium bicarbonate solution (100 mL) and brine (50 mL), and then the solution was dried over MgSO4
- concentrationconcentrated to a residue
- customThe crude product was purified by silica gel chromatography (120 g of silica)
- washeluting with a gradient of 40% to 100% ethyl acetate in hexanes
Sources & evidence
- ORD record
- ord-8c29eb896c0140ad8a7fb02bfb9fff0d
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09221796B2
Reaction notes
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