2,6-Lutidine → 3-[(3-Chloro-4-trifluoromethoxy-phenyl)-methoxycarbonylmethyl-amino]-propionic acid tert-butyl ester

HRID 2095516Notes

Reaction equation

HRID 2095516 reaction equation
[C:1]([O:5][C:6](=[O:22])[CH2:7][CH2:8][NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[C:12]([Cl:21])[CH:11]=1)([CH3:4])([CH3:3])[CH3:2].Br[CH2:24][C:25]([O:27][CH3:28])=[O:26].N1C(C)=CC=CC=1C>CC#N>[C:1]([O:5][C:6](=[O:22])[CH2:7][CH2:8][N:9]([C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:19])([F:20])[F:18])=[C:12]([Cl:21])[CH:11]=1)[CH2:24][C:25]([O:27][CH3:28])=[O:26])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 60984Methyl bromoacetateHCID 670747983-(3-Chloro-4-trifluoromethoxy-phenylamino)-propionic acid tert-butyl ester

Product 1

HCID 670744093-[(3-Chloro-4-trifluoromethoxy-phenyl)-methoxycarbonylmethyl-amino]-propionic acid tert-butyl esterYield 64.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
115 °C

Procedure

A neat solution of 8.50 g (22.5 mmol) of 3-(3-chloro-4-trifluoromethoxy-phenylamino)-propionic acid tert-butyl ester, 10.71 ml (112.6 mmol) of methyl bromoacetate and 13.07 ml (112.6 mmol) of 2,6-lutidine was stirred 14 h at 60° C., diluted with 30 ml of CH3CN and heated at 115° C. for 20 h. The reaction was then partitioned between aqueous 10% KHSO4 solution and EtOAc (3×). The organic phases were washed with aqueous 10% NaCl, dried over Na2SO4 evaporated and purified by flash silica gel column (n-heptane:EtOAc 95:5 to 85:1) to yield 5.94 g (64%) of the title compound as light yellow oil. MS: 412.11 (MH+, Cl).

Workup

  1. customThe reaction was then partitioned between aqueous 10% KHSO4 solution and EtOAc (3×)
  2. washThe organic phases were washed with aqueous 10% NaCl
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. custompurified by flash silica gel column (n-heptane:EtOAc 95:5 to 85:1)

Sources & evidence

ORD record
ord-e01a19749e944c1f8eb1c880eeb5e47f
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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