2,6-Lutidine → 3-(3-Chloro-4-trifluoromethoxy-phenylamino)-propionic acid tert-butyl ester

HRID 2095515Notes

Reaction equation

HRID 2095515 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH2:13])[CH:5]=[CH:6][C:7]=1[O:8][C:9]([F:12])([F:11])[F:10].N1C(C)=CC=CC=1C.Br[CH2:23][CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26]>C1(C)C=CC=CC=1>[C:28]([O:27][C:25](=[O:26])[CH2:24][CH2:23][NH:13][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]([F:11])([F:12])[F:10])=[C:2]([Cl:1])[CH:3]=1)([CH3:31])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 256128tert-Butyl 3-bromopropionateHCID 27738433-Chloro-4-(trifluoromethoxy)aniline

Product 1

HCID 670747983-(3-Chloro-4-trifluoromethoxy-phenylamino)-propionic acid tert-butyl esterYield 66.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 9.26 g (42.4 mmol) of 3-chloro-4-trifluoromethoxy-phenylamine and 4.39 ml (42.4 mmol) of 2,6-lutidine in 50 ml of toluene was treated slowly with 7.30 ml (42.4 mmol) of tert-butyl 3-bromopropionate and stirred 2 days at reflux temperature. The reaction was then partitioned between aqueous 10% KHSO4 and EtOAc (3×). The organic phases were washed with 10% NaCl, dried over Na2SO4 evaporated and purified by flash silica gel column (n-heptane:EtOAc 9:1) to yield 9.59 g (60%) of the title compound as brown liquid. MS: 339 (M+, Cl).

Workup

  1. temperatureat reflux temperature
  2. customThe reaction was then partitioned between aqueous 10% KHSO4 and EtOAc (3×)
  3. washThe organic phases were washed with 10% NaCl
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. custompurified by flash silica gel column (n-heptane:EtOAc 9:1)

Sources & evidence

ORD record
ord-17ec8106e27a47cf970213d984b94604
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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