Water → 4-{2-[(3-Bromo-4-chloro-benzoyl)-methyl-amino]-3-methyl-phenoxy}-butyric acid tert-butyl ester

HRID 1485931Notes

Reaction equation

HRID 1485931 reaction equation
[C:1]([O:5][C:6](=[O:29])[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH3:17])[C:12]=1[NH:18][C:19](=[O:28])[C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Br:27])[CH:21]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:33].O>CN(C=O)C>[C:1]([O:5][C:6](=[O:29])[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH3:17])[C:12]=1[N:18]([C:19](=[O:28])[C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Br:27])[CH:21]=1)[CH3:33])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 686025154-[2-(3-Bromo-4-chloro-benzoylamino)-3-methyl-phenoxy]-butyric acid tert-butyl ester

Product 1

HCID 686028104-{2-[(3-Bromo-4-chloro-benzoyl)-methyl-amino]-3-methyl-phenoxy}-butyric acid tert-butyl esterYield 89.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[2-(3-bromo-4-chloro-benzoylamino)-3-methyl-phenoxy]-butyric acid tert-butyl ester (10.2 g, 21.3 mmol) in dry DMF (100 mL) at 0° C. under N2, NaH (60% in mineral oil, 1.7 g, 42.6 mmol) was added in several portions with stirring. 10 minutes later, iodomethane (2.0 mL, 32.1 mmol) was added. The mixture was warmed to room temperature by removal of ice bath and stirring was continued for 1 hr. Water (10 mL) was then added and organics were extracted by ethyl acetate, which was then washed by water and brine, and was dried over MgSO4. After concentration, the crude product was purified by silica gel chromatography eluting with ethyl acetate/hexane (1/4) to yield 4-{2-[(3-bromo-4-chloro-benzoyl)-methyl-amino]-3-methyl-phenoxy}-butyric acid tert-butyl ester (9.5 g).

Workup

  1. stirringstirring
  2. extractionorganics were extracted by ethyl acetate, which
  3. washwas then washed by water and brine
  4. dry with materialwas dried over MgSO4
  5. concentrationAfter concentration
  6. customthe crude product was purified by silica gel chromatography
  7. washeluting with ethyl acetate/hexane (1/4)

Sources & evidence

ORD record
ord-76489c7d44754455a2ae4be853fb5c8d
Source dataset
uspto-grants-2016_08
Patent number
US09422310B2

Reaction notes

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