Water → HCID 14850319, compound

HRID 1651128Notes

Reaction equation

HRID 1651128 reaction equation
[CH:1]1([CH3:34])[CH2:6][CH2:5][CH:4]([CH:7]([CH3:9])[CH3:8])[CH:3]([O:10][C:11]([CH:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16](=[O:23])[N:15]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([Br:31])=[CH:27][C:26]=3[F:32])[C:14]2=[O:33])=[O:12])[CH2:2]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44].O>CN(C=O)C>[CH3:47][C:46]([O:45][C:43](=[O:44])[CH2:42][C:13]1([C:11]([O:10][CH:3]2[CH:4]([CH:7]([CH3:8])[CH3:9])[CH2:5][CH2:6][CH:1]([CH3:34])[CH2:2]2)=[O:12])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16](=[O:23])[N:15]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([Br:31])=[CH:27][C:26]=2[F:32])[C:14]1=[O:33])([CH3:49])[CH3:48]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 79177tert-Butyl bromoacetateHCID 14850317HCID 14850317, compound

Product 1

HCID 14850319HCID 14850319, compoundYield 25.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of 2-[(4-bromo-2-fluorophenyl)methyl]-1,2,3,4-tetrahydro-1,3-dioxo-4-isoquinoline carboxylic acid menthyl ester (7.62 g, 14.37 mmol), K2CO3 (3.96 g, 28.74 mmol) in DMF (100 mL) was added tert-butyl bromoacetate (4.64 mL, 28.74 mmol). The mixture was stirred at 85° C. for 2 hours, poured into H2O (1000 mL) and extracted with EtOAc. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography (hexane/EtOAc:4/1) gave a clear oil (6.9 g, diastereomeric mixture). The two diastereomers were separated by preparative HPLC on prep. Pac silica column, (μ poraSi/125 Å, 15-20 μsilica) by elution with hexane/CH2Cl2 to give the less polar A-diastereomer as a white solid (2.4 g) and the more polar diastereomer B as a clear oil (2.2 g). The diastereomeric purity was determined by analytical HPLC, on Dynamax silica 25 cmx4.1 mm and was found to be greater than 99% for both diastereomers.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic extracts were dried over MgSO4
  3. customEvaporation and purification by flash chromatography (hexane/EtOAc:4/1)
  4. customgave a clear oil (6.9 g, diastereomeric mixture)
  5. customThe two diastereomers were separated by preparative HPLC on prep
  6. washPac silica column, (μ poraSi/125 Å, 15-20 μsilica) by elution with hexane/CH2Cl2

Sources & evidence

ORD record
ord-d5f246f517304078b7bf162b7d1681ba
Source dataset
uspto-grants-1990_05
Patent number
US04927831

Reaction notes

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