Citric Acid → Isopropyl ((2S,4R)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-YL)carbamate

HRID 2201327Notes

Reaction equation

HRID 2201327 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>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[NH:8][C@@H:9]([CH3:20])[CH2:10][C@H:11]2[NH:13][C:14](=[O:19])[O:15][CH:16]([CH3:18])[CH3:17]

Participants

9

Reactant 5

HCID 311Citric AcidHCID 313Hydrochloric AcidHCID 24644Magnesium chloride hexahydrateHCID 4311764Sodium borohydrideHCID 681848681-Methylethyl{(3S)-3-[(4-bromophenyl)amino]butanoyl}carbamate

Product 1

HCID 70331708Isopropyl ((2S,4R)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-YL)carbamate

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

1-methylethyl {(3S)-3-[(4-bromophenyl)amino]butanoyl}carbamate (for a preparation see Intermediate 14) (17.9 g, 52.2 mmol) was taken up in Ethanol (150 mL) and cooled to below −10° C. (internal) 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 hr then warmed to RT and stirred for an hour. The resulting thick suspension was poured into a mixture of citric acid (25.05 g, 130 mmol), HCl (205 mL, 205 mmol) and Dichloromethane (DCM) (205 mL). The biphasic mixture was stirred at RT for 1 hr. LCMS showed no SM remained so the organic layer was extracted and dried with Na2SO4, filtered and concentrated to yield the product as a light brown solid (14.1 g). LCMS (Method B): Rt=1.13, MH+=327

Workup

  1. temperaturecooled to below −10° C. (internal) in a CO2/acetone bath
  2. customthe temperature below −5° C
  3. stirringstirred for an hour
  4. stirringThe biphasic mixture was stirred at RT for 1 hr
  5. extractionwas extracted
  6. dry with materialdried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-43b898f8ac56412daabded3df554f13d
Source dataset
uspto-grants-2016_06
Patent number
US09360482B2

Reaction notes

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