Sodium borohydride → Tert-butyl {1-[5-chloro-2-methoxy-4-methyl-3-(5-oxopyrrolidin-3-yl)phenyl]ethyl}carbamate

HRID 511017Notes

Reaction equation

HRID 511017 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[C:12]([O:29][CH3:30])=[C:13]([CH:19]([CH2:25][N+:26]([O-])=O)[CH2:20][C:21]([O:23]C)=O)[C:14]([CH3:18])=[C:15]([Cl:17])[CH:16]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO.O.O.O.O.O.O.[Ni](Cl)Cl>[Cl:17][C:15]1[C:14]([CH3:18])=[C:13]([CH:19]2[CH2:20][C:21](=[O:23])[NH:26][CH2:25]2)[C:12]([O:29][CH3:30])=[C:11]([CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])[CH3:10])[CH:16]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 86666937Methyl 3-(3-{1-[(tert-butoxycarbonyl)amino]ethyl}-5-chloro-2-methoxy-6-methylphenyl)-4-nitrobutanoate

Product 1

HCID 86666939Tert-butyl {1-[5-chloro-2-methoxy-4-methyl-3-(5-oxopyrrolidin-3-yl)phenyl]ethyl}carbamate

Reagents, catalysts & solvents 2

HCID 11791229Dichloronickel;hexahydrateCatalystHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of methyl 3-(3-{1-[(tert-butoxycarbonyl)amino]ethyl}-5-chloro-2-methoxy-6-methylphenyl)-4-nitrobutanoate (0.92 g, 2.1 mmol) in methanol (15 mL) was treated with nickel chloride hexahydrate (0.99 g, 4.1 mmol) and stirred for 5 minutes. The reaction mixture was cooled to 0° C. and treated with sodium tetrahydroborate (0.84 g, 22 mmol) in four portions. The ice bath was removed and the reaction mixture was stirred for 30 min and heated at 60° C. for 4.5 hours. The reaction mixture was diluted with saturated sodium bicarbonate (20 mL) and EtOAc (50 mL) and filtered over Celite. The Celite was washed with EtOAc and the filtrate was concentrated to give the desired product as a mixture of diastereoisomers at the lactam carbon. The mixture of diastereoisomers was separated by chiral HPLC (ChiralPak AD-H column, 20×250 mm, 5 micron particle size, eluting with 60% ethanol in hexanes at 9 mL/min, column loading ˜3 mg/injection) to give peak 1 (0.39 g, 49%, retention time: 6.25 min) and peak 2 (0.32 g, 40%, retention time: 9.34 min) as white solids.

Workup

  1. customThe ice bath was removed
  2. stirringthe reaction mixture was stirred for 30 min
  3. temperatureheated at 60° C. for 4.5 hours
  4. additionThe reaction mixture was diluted with saturated sodium bicarbonate (20 mL) and EtOAc (50 mL)
  5. filtrationfiltered over Celite
  6. washThe Celite was washed with EtOAc
  7. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-381d8bd6e83a4a878e971b89d83e688f
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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