Dimethyl Sulfoxide → 3-[(3-Chloro-4-trifluoromethoxy-phenyl)-(2-oxo-ethyl)-amino]-propionic acid tert-butyl ester

HRID 2095518Notes

Reaction equation

HRID 2095518 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16](=[O:35])[CH2:17][CH2:18][N:19]([C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[C:25]([Cl:34])[CH:24]=1)[CH2:20][CH2:21][OH:22])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C.OP([O-])(O)=O.[K+]>C(Cl)Cl>[C:11]([O:15][C:16](=[O:35])[CH2:17][CH2:18][N:19]([C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:32])([F:33])[F:31])=[C:25]([Cl:34])[CH:24]=1)[CH2:20][CH:21]=[O:22])([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516951Monobasic potassium phosphateHCID 670740073-[(3-Chloro-4-trifluoromethoxy-phenyl)-(2-hydroxy-ethyl)-amino]-propionic acid tert-butyl ester

Product 1

HCID 866526903-[(3-Chloro-4-trifluoromethoxy-phenyl)-(2-oxo-ethyl)-amino]-propionic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-5 °C

Procedure

To a solution of 0.55 ml (6.3 mmol) of oxalyl chloride in 21 ml CH2Cl2 at −50 to −60° C. was added a solution of 0.93 ml (13.1 mmol) dimethylsulfoxide in 7 ml of CH2Cl2 within 20 min. The solution was stirred for 5 min, then a solution of 2.10 g (5.5 mmol) of 3-[(3-chloro-4-trifluoromethoxy-phenyl)-(2-hydroxy-ethyl)-amino]-propionic acid tert-butyl ester in 14 ml CH2Cl2 was added within 20 min. The mixture was stirred for 15 min and 3.81 ml (27.4 mmol) of triethylamine were added within 20 min. The suspension was stirred for 3 h and slowly warmed to −5° C. The reaction was neutralized with cold aqueous 10% KH2PO4 (adjusted with solid KH2PO4 to pH 4-5) and extracted with EtOAc (3×). The organic phases were washed with aqueous saturated NaHCO3 (freshly prepared), aqueous 10% NaCl, dried over Na2SO4 evaporated to yield 2.21 g (quantitative) of the title compound as yellow oil. MS: 381 (M+, Cl).

Workup

  1. stirringThe mixture was stirred for 15 min
  2. stirringThe suspension was stirred for 3 h
  3. extractionextracted with EtOAc (3×)
  4. washThe organic phases were washed with aqueous saturated NaHCO3 (
  5. customfreshly prepared), aqueous 10% NaCl
  6. dry with materialdried over Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-9bdc09a5c69d47f0b58fb9d763f4e6df
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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