Acetone → 3-[(3-Chloro-4-trifluoromethoxy-phenyl)-(2-hydroxy-ethyl)-amino]-propionic acid tert-butyl ester

HRID 2095517Notes

Reaction equation

HRID 2095517 reaction equation
[C:1]([O:5][C:6](=[O:27])[CH2:7][CH2:8][N:9]([C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[C:17]([Cl:26])[CH:16]=1)[CH2:10][C:11](OC)=[O:12])([CH3:4])([CH3:3])[CH3:2].[Li+].[BH4-].CO.CC(C)=O>C1COCC1.C1CCCCC1.[OH-].[Na+]>[C:1]([O:5][C:6](=[O:27])[CH2:7][CH2:8][N:9]([C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]([F:24])([F:25])[F:23])=[C:17]([Cl:26])[CH:16]=1)[CH2:10][CH2:11][OH:12])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 180AcetoneHCID 887MethanolHCID 4148881Lithium borohydrideHCID 670744093-[(3-Chloro-4-trifluoromethoxy-phenyl)-methoxycarbonylmethyl-amino]-propionic acid tert-butyl ester

Product 1

HCID 670740073-[(3-Chloro-4-trifluoromethoxy-phenyl)-(2-hydroxy-ethyl)-amino]-propionic acid tert-butyl esterYield 78.9%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8078CyclohexaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of 3.00 g (7.3 mmol) of 3-[(3-chloro-4-trifluoromethoxy-phenyl)-methoxycarbonylmethyl-amino]-propionic acid tert-butyl ester in 20 ml of THF was treated with 4.44 ml (8.9 mmol) of LiBH4 (2 M in THF) and 0.59 ml (14.6 mmol) of MeOH (with cooling bath at RT). The reaction was stirred for 2 h at RT, cooled to 0° C. and stopped with 2 ml of acetone. The reaction was diluted with 4.5 ml of cyclohexane, 18 ml of aqueous 2 N NaOH were added and after 30 min extracted with EtOAc (3×). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4) and evaporated to give after flash silica gel column (EtOAc:n-heptane 1:4 to 1:1) 2.21 g (78%) of the titled compound as light yellow oil. MS: 384.12 (MH+, Cl).

Workup

  1. temperaturecooled to 0° C.
  2. additionwere added and after 30 min
  3. extractionextracted with EtOAc (3×)
  4. washThe organic phases were washed with aqueous 10% NaCl
  5. dry with materialdried (Na2SO4)
  6. customevaporated

Sources & evidence

ORD record
ord-1548d41ac6434763a718694acccc2af7
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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