Trifluoroacetic acid → 2-((S)-2-{(R)-2-amino-2-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-acetylamino}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester

HRID 2222979Notes

Reaction equation

HRID 2222979 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:47])[C@@H:12]([NH:20][C:21](=[O:46])[C@H:22]([NH:38]C(OC(C)(C)C)=O)[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:30][C@H:31]3[CH2:35][O:34]C(C)(C)[O:32]3)=[CH:25][CH:24]=2)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[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:47])[C@@H:12]([NH:20][C:21](=[O:46])[C@H:22]([NH2:38])[C:23]2[CH:24]=[CH:25][C:26]([O:29][CH2:30][C@H:31]([OH:32])[CH2:35][OH:34])=[CH:27][CH:28]=2)[CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[S:8][CH:9]=1)=[O:4]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866040552-((S)-2-{(R)-2-tert-butoxycarbonylamino-2-[4-((S)-2,2-dimethyl-[1,3]dioxolan4-ylmethoxy)-phenyl]-acetylamino}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester

Product 1

HCID 866040562-((S)-2-{(R)-2-amino-2-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-acetylamino}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl esterYield 90.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-((S)-2-{(R)-2-tert-butoxycarbonylamino-2-[4-((S)-2,2-dimethyl-[1,3]dioxolan4-ylmethoxy)-phenyl]-acetylamino}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester (170 mg, 0.25 mmol) in dichloromethane (2.0 mL) was added trifluoroacetic acid (0.5 mL, 6.5 mmol) at 0° C. The reaction was warmed to room temperature and stirred for 4 hours. The solvent was removed under vacuum and the residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with ethyl acetate and the extracts were combined, washed with brine and dried over sodium sulfate to give 2-((S)-2-{(R)-2-amino-2-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-acetylamino}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester as a foam (120 mg, 90%).

Workup

  1. customThe solvent was removed under vacuum
  2. customthe residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-339f6136853f4b69b4b6cf2a9275658d
Source dataset
uspto-grants-2008_05
Patent number
US07371869B2

Reaction notes

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