N-Benzyloxycarbonyl-4-[(3R)-3-amino-1-oxo-4-(phenylthio)butyl]morpholine → (R)-3-amino-1-morpholino-4-(phenylthio)butan-1-one
Reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7](=[O:29])[CH2:8][C@@H:9]([NH:18]C(=O)OCC2C=CC=CC=2)[CH2:10][S:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:3][CH2:2]1>Br.C(O)(=O)C>[NH2:18][C@@H:9]([CH2:10][S:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:8][C:7]([N:4]1[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)=[O:29]Participants
4
Procedure
A suspension of (R)-benzyl 4-morpholino-4-oxo-1-(phenylthio)butan-2-ylcarbamate (INTERMEDIATE 71, 25 g, 60 mmol) in 40% HBr in acetic acid (500 ml) was stirred at room temperature for 50 hrs. The reaction mixture became homogeneous during this time. The reaction mixture was concentrated to dryness, diluted with water (400 ml) and 5% aq. HCl (200 ml) and washed with diethyl ether (3×100 ml). The aqueous phase was brought to pH ˜8-9 with solid Na2CO3 and extracted vigorously with CH2Cl2 (5×). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure to give the title product (16.9 g, yield: almost quantitative), which was used in the preparation of Intermediate 73 without further purification.
Workup
- concentrationThe reaction mixture was concentrated to dryness
- additiondiluted with water (400 ml) and 5% aq. HCl (200 ml)
- washwashed with diethyl ether (3×100 ml)
- extractionextracted vigorously with CH2Cl2 (5×)
- dry with materialThe combined organic layers were dried (MgSO4)
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-ce9656db307c46648448a2e4ea29308b
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09018381B2
Reaction notes
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