Trifluoroacetic acid → 2-{(2S,3S)-2-[(R)-2-amino-2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester

HRID 32830

Reaction equation

HRID 32830 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:43])[C@@H:12]([NH:21][C:22](=[O:42])[C@H:23]([NH:34]C(OC(C)(C)C)=O)[C:24]2[CH:33]=[CH:32][C:27]3[O:28][CH2:29][CH2:30][O:31][C:26]=3[CH:25]=2)[C@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:14])[S:8][CH:9]=1)=[O:4].FC(F)(F)C(O)=O>ClCCl>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:43])[C@@H:12]([NH:21][C:22](=[O:42])[C@H:23]([NH2:34])[C:24]2[CH:33]=[CH:32][C:27]3[O:28][CH2:29][CH2:30][O:31][C:26]=3[CH:25]=2)[C@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:14])[S:8][CH:9]=1)=[O:4]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866033912-{(2S,3S)-2-[(R)-2-tert-butoxycarbonylamino-2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester

Product 1

HCID 866033922-{(2S,3S)-2-[(R)-2-amino-2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl esterYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-{(2S,3S)-2-[(R)-2-tert-Butoxycarbonylamino-2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester (0.49 g, 0.80 mmol) was stirred in dichloromethane (8 mL) in an ice bath. Trifluoroacetic acid (8 mL) was added and the solution was stirred for 2 hours. The reaction mixture was evaporated and the residue was precipitated with hexanes/ether. The mixture was stirred vigorously for 10 minutes and then filtered. The resulting solid was partitioned between aqueous sodium bicarbonate and dichloromethane. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic extracts were washed with brine and dried (sodium sulfate). Evaporation of the solvents gave 2-{(2S,3S)-2-[(R)-2-amino-2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester (0.384 g, 94%).

Workup

  1. customThe reaction mixture was evaporated
  2. customthe residue was precipitated with hexanes/ether
  3. stirringThe mixture was stirred vigorously for 10 minutes
  4. filtrationfiltered
  5. customThe resulting solid was partitioned between aqueous sodium bicarbonate and dichloromethane
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with dichloromethane
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried (sodium sulfate)
  10. customEvaporation of the solvents

Sources & evidence

ORD record
ord-1c9139199018457ab1988528d830d222
Source dataset
uspto-grants-2008_09
Patent number
US07427635B2

Linked notes

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