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

HRID 448885Notes

Reaction equation

HRID 448885 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[Cl:24])[C:5]([N:7]([CH3:20])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[O:6].C(Cl)(=O)C(Cl)=O.[C:31](O)([CH3:34])([CH3:33])[CH3:32]>C(Cl)Cl>[C:31]([O:18][C:17](=[O:19])[CH2:16][CH2:15][CH2:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[N:7]([C:5](=[O:6])[C:4]1[CH:21]=[CH:22][C:23]([Cl:24])=[C:2]([Br:1])[CH:3]=1)[CH3:20])([CH3:34])([CH3:33])[CH3:32]

Participants

5

Reactant 3

HCID 6386tert-ButanolHCID 65578Oxalyl chlorideHCID 686025894-{2-[(3-Bromo-4-chloro-benzoyl)-methyl-amino]-phenyl}-butyric acid

Product 1

HCID 686027474-{2-[(3-Bromo-4-chloro-benzoyl)-methyl-amino]-phenyl}-butyric acid tert-butyl esterYield 90.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a cooled solution (0° C.) of 4-{2-[(3-bromo-4-chloro-benzoyl)-methyl-amino]-phenyl}-butyric acid (1.07 g, 2.60 mmol) in anhydrous DCM (10 mL), oxalyl chloride (0.34 mL, 3.90 mmol) was added dropwise. The mixture was stirred at room temperature for 4 hours, concentrated in vacuo and redissolved in anhydrous dichloromethane (5 mL). A solution of t-butanol (960 mg, 13 mmol) in anhydrous DCM (5 mL) was added and the mixture was stirred at room temperature overnight. After dilution with DCM, the mixture was washed with sat NaHCO3 and brine, dried over Na2SO4, filtered and concentrated. Purification by silica gel column chromatography (EtOAc/Hexanes: 1/4 with gradient up to EtOAc/Hexanes 1/3) afforded 1.1 g of 4-{2-[(3-bromo-4-chloro-benzoyl)-methyl-amino]-phenyl}-butyric acid tert-butyl ester as a colorless oil. MS [M+H]+ (fragment): 411.7 (f; tR=3.10 min, (method 1)

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionredissolved in anhydrous dichloromethane (5 mL)
  3. stirringthe mixture was stirred at room temperature overnight
  4. washAfter dilution with DCM, the mixture was washed with sat NaHCO3 and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel column chromatography (EtOAc/Hexanes: 1/4 with gradient up to EtOAc/Hexanes 1/3)

Sources & evidence

ORD record
ord-a12e95e0ba2b43918ca781b820291455
Source dataset
uspto-grants-2013_07
Patent number
US08481738B2

Reaction notes

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