Potassium Carbonate → 4-[2-(3-Bromo-4-chloro-benzoylamino)-3-methyl-phenoxy]-butyric acid tert-butyl ester

HRID 661616Notes

Reaction equation

HRID 661616 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[Cl:19])[C:5]([NH:7][C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=1[OH:15])=[O:6].Br[CH2:21][CH2:22][CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:27]([O:26][C:24](=[O:25])[CH2:23][CH2:22][CH2:21][O:15][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]([CH3:14])[C:8]=1[NH:7][C:5](=[O:6])[C:4]1[CH:16]=[CH:17][C:18]([Cl:19])=[C:2]([Br:1])[CH:3]=1)([CH3:30])([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2757253tert-Butyl 4-bromobutanoateHCID 686028573-bromo-4-chloro-N-(2-hydroxy-6-methyl-phenyl)-benzamide

Product 1

HCID 686025154-[2-(3-Bromo-4-chloro-benzoylamino)-3-methyl-phenoxy]-butyric acid tert-butyl esterYield 63.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-bromo-4-chloro-N-(2-hydroxy-6-methyl-phenyl)-benzamide (11.3 g, 33.2 mmol), t-butyl 4-bromobutyrate (8.2 g, 36.6 mmol) and K2CO3 (9.2 g, 66.5 mmol) was heated in DMF (100 mL) at 60° C. for 14 hrs. The mixture was then concentrated to remove DMF and partitioned between ethyl acetate and water. The organic layer was separated and washed with water and brine, dried over MgSO4, then purified by silica gel column chromatography eluting with ethyl acetate/hexane (1/4) to yield a red solid, which was further washed with ether to produce a white powder as 4-[2-(3-bromo-4-chloro-benzoylamino)-3-methyl-phenoxy]-butyric acid tert-butyl ester (10.2 g). MS [M−(t-Bu)+H]+: 425.8/427.8; tR=2.79 min. (method 1)

Workup

  1. concentrationThe mixture was then concentrated
  2. customto remove DMF
  3. custompartitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. washwashed with water and brine
  6. dry with materialdried over MgSO4
  7. custompurified by silica gel column chromatography
  8. washeluting with ethyl acetate/hexane (1/4)
  9. customto yield a red solid, which
  10. washwas further washed with ether

Sources & evidence

ORD record
ord-bf5009e320bf4cb3a1c4157fe2941227
Source dataset
uspto-grants-2011_12
Patent number
US08084614B2

Reaction notes

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