Trimethylsilyl cyanide → (S)-2-((R)-2-hydroxy-1-phenylethylamino)-2-(1-methylcyclopropyl)acetonitrile
Reaction equation
[CH3:1][C:2]1([CH:5]=O)[CH2:4][CH2:3]1.[NH2:7][C@H:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:9][OH:10].C[Si]([C:21]#[N:22])(C)C>CO>[OH:10][CH2:9][C@H:8]([NH:7][C@@H:5]([C:2]1([CH3:1])[CH2:3][CH2:4]1)[C:21]#[N:22])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1Participants
Procedure
To a solution of 1-methylcyclopropanecarbaldehyde in MeOH (20 mL) was added (R)-2-amino-2-phenylethanol (3.23 g, 23.54 mmol) at rt under N2 in 3 portions. The mixture was stirred at rt for 2 h and then cooled down with ice-water bath and added with trimethylsilyl cyanide (5.74 mL, 42.8 mmol) dropwise over 5 min. The mixture was stirred for 10 min, ice bath was removed and the reaction was stirred at rt overnight. The reaction mixture was concentrated and purified on a 40 g silica gel column (EtOAc/hexane: 0 to 100%) to afford (S)-2-((R)-2-hydroxy-1-phenylethylamino)-2-(1-methylcyclopropyl)acetonitrile. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.40-7.30 (m, 5H), 4.08 (dd, J=9.2, 4.1 Hz, 1H), 3.82 (dd, J=10.8, 4.0 Hz, 1H), 3.64 (t, J=10.0 Hz, 1H), 2.97 (s, 1H), 1.26 (s, 3H), 0.63-0.53 (m, 2H), 0.51-0.42 (m, 2H).
Workup
- temperaturecooled down with ice-water bath
- stirringThe mixture was stirred for 10 min
- customice bath was removed
- stirringthe reaction was stirred at rt overnight
- concentrationThe reaction mixture was concentrated
- custompurified on a 40 g silica gel column (EtOAc/hexane: 0 to 100%)
Sources & evidence
- ORD record
- ord-3c7d8aaeb009425fae92efd3b5df1c62
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09326973B2
Reaction notes
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