Water → {3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydrobenzooxazol-5-yl)-propyl]-benzoylamino}-acetic acid tert-butyl ester

HRID 2096905Notes

Reaction equation

HRID 2096905 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH:11]([CH3:29])[C:12]([OH:28])([C:17]1[CH:18]=[CH:19][C:20]2[O:24][C:23](=[O:25])[N:22]([CH3:26])[C:21]=2[CH:27]=1)[C:13]([F:16])([F:15])[F:14])[C:5](O)=[O:6].[NH2:30][C@H:31]([C:36]([O-:38])=[O:37])C(C)(C)C.O>CN(C=O)C>[C:4]([O:38][C:36](=[O:37])[CH2:31][NH:30][C:5](=[O:6])[C:4]1[CH:8]=[CH:9][C:10]([CH:11]([CH3:29])[C:12]([OH:28])([C:17]2[CH:18]=[CH:19][C:20]3[O:24][C:23](=[O:25])[N:22]([CH3:26])[C:21]=3[CH:27]=2)[C:13]([F:15])([F:14])[F:16])=[C:2]([Cl:1])[CH:3]=1)([CH3:8])([CH3:5])[CH3:3]

Participants

5

Reactant 3

HCID 962WaterHCID 666971253-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-benzoic acidHCID 77068310tert-Butylglycinate

Product 1

HCID 66697004{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydrobenzooxazol-5-yl)-propyl]-benzoylamino}-acetic acid tert-butyl esterYield 199.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-propyl]-benzoic acid (80 mg) and 1,1-carbonyldiimidazole (45 mg) were dissolved in dry DMF (2.0 mL) and stirred at 50° C. for 1 hour. The mixture was cooled to r.t. and a solution of tert-butylglycinate (391 mg) in DMF (0.7 mL) was added drop by drop. Stirring was then continued for 2 hours. The reaction mixture was poured into a mixture of water and ice and the aqueous phase was extracted with ethyl acetate. The organic extracts were washed with brine, dried over Na2SO4 and evaporated. The residue was purified by flash chromatography (silica gel, gradient of ethyl acetate in heptane) to provide the title compound {3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(3-methyl-2-oxo-2,3-dihydrobenzooxazol-5-yl)-propyl]-benzoylamino}-acetic acid tert-butyl ester as a colorless solid (101 mg). MS (m/e)=560.3 [M+NH4+].

Workup

  1. temperatureThe mixture was cooled to r.t.
  2. stirringStirring
  3. waitwas then continued for 2 hours
  4. extractionthe aqueous phase was extracted with ethyl acetate
  5. washThe organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customThe residue was purified by flash chromatography (silica gel, gradient of ethyl acetate in heptane)

Sources & evidence

ORD record
ord-90a8991d5f1f4f619deb4ad3e5bce2de
Source dataset
uspto-grants-2013_05
Patent number
US08450313B2

Reaction notes

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