Citric Acid → Isopropyl ((2S,4R)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-YL)carbamate
Reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C@@H:9]([CH3:20])[CH2:10][C:11]([NH:13][C:14](=[O:19])[O:15][CH:16]([CH3:18])[CH3:17])=O)=[CH:4][CH:3]=1.[BH4-].[Na+].O.O.O.O.O.O.[Cl-].[Mg+2].[Cl-].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.Cl>C(O)C.O.ClCCl>[CH3:17][CH:16]([O:15][C:14](=[O:19])[NH:13][C@H:11]1[C:6]2[C:5](=[CH:4][CH:3]=[C:2]([Br:1])[CH:7]=2)[NH:8][C@@H:9]([CH3:20])[CH2:10]1)[CH3:18]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 3
Procedure
1-Methylethyl {(3S)-3-[(4-bromophenyl)amino]butanoyl}carbamate (for a preparation see Intermediate 102) (17.9 g, 52.2 mmol) was taken up in ethanol (150 mL) and cooled to below −10° C. (internal temperature) in a CO2/acetone bath. NaBH4 (1.381 g, 36.5 mmol) was added followed by magnesium chloride hexahydrate (11.35 g, 55.8 mmol) in water (25 mL) keeping the temperature below −5° C. The mixture was allowed to stir at <0° C. for 1 h then warmed to room temperature and stirred for an hour. The resulting thick suspension was poured into a mixture of citric acid (25.05 g, 130 mmol), HCl (1M in water, 205 mL, 205 mmol) and dichloromethane (DCM) (205 mL). The biphasic mixture was stirred at room temperature for 1 h. LCMS showed no remaining starting material so the layers were separated and the organic layer dried with Na2SO4, filtered and concentrated to yield the product as a light brown solid (14.1 g).
Workup
- temperaturecooled to below −10° C. (internal temperature) in a CO2/acetone bath
- customthe temperature below −5° C
- stirringstirred for an hour
- stirringThe biphasic mixture was stirred at room temperature for 1 h
- customwere separated
- dry with materialthe organic layer dried with Na2SO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-10360ee8734a4f6cac2ae80d53e8bf84
- Source dataset
- uspto-grants-2013_11
- Patent number
- US08580957B2
Reaction notes
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