Trifluoroacetic acid → N-[(2R)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]-N-[(2S)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]amine

HRID 402989Notes

Reaction equation

HRID 402989 reaction equation
C(OC([NH:8][C@H:9]([CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[CH2:10][N:11]([CH2:29][C@@H:30]([NH:38]C(OC(C)(C)C)=O)[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)C(OCC1C2C=CC=CC=2C2C1=CC=CC=2)=O)=O)(C)(C)C.FC(F)(F)[C:55]([OH:57])=[O:56].[C:60](=[O:78])([O:71][CH2:72][C:73]1[S:77][CH:76]=[N:75][CH:74]=1)OC1C=CC([N+]([O-])=O)=CC=1>ClCCl.C(OCC)(=O)C>[S:77]1[C:73]([CH2:72][O:57][C:55]([NH:38][C@H:30]([CH2:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:29][NH:11][CH2:10][C@@H:9]([NH:8][C:60]([O:71][CH2:72][C:73]2[S:77][CH:76]=[N:75][CH:74]=2)=[O:78])[CH2:46][C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)=[O:56])=[CH:74][N:75]=[CH:76]1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 98821474-Nitrophenyl 1,3-thiazol-5-ylmethyl carbonateHCID 60204743N-[(2R)-2-(tert-butoxycarbonylamino)3-phenylpropyl]-N-[(2S)-2-(tert-butoxycarbonylamino)-3-phenylpropyl]-N-[9-fluorenylmethoxycarbonyl]amine

Product 1

HCID 60204702N-[(2R)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]-N-[(2S)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]amineYield 30%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The product from Example 26C (952 mg, 1.35 mmol) in dichloromethane (20 mL) was treated with trifluoroacetic acid (10 mL) at ambient temperature. After stirring for one hour, the mixture was concentrated. The residue was immersed in an aqueous solution of 10% K2CO3 (10 mL) and extracted with ethyl acetate (3×10 mL). The organic phases were combined and treated with a solution of 4-nitrophenyl 1,3-thiazol-5-ylmethyl carbonate [prepared from 4-nitrophenyl 1,3-thiazol-5-ylmethyl carbonate hydrochloride salt (857 mg, 2.71 mmol, 2.0 eq) by extraction with aqueous NaHCO3] in ethyl acetate (5 mL) at ambient temperature. After stirring for 1 hour, the mixture was washed with aqueous 10% K2CO3 (5×25 mL), brine (25 mL), dried over sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by flash column chromatography on silica gel eluting with (chloroform:methanol, 98:2) to provide the title compound (0.39, 30%). 1H NMR (CDCl3) δ 8.78 (s, 2H), 7.84 (s, 2H), 7.33-7.04 (m, 10H), 5.00-4.86 (m, 4H), 3.98-3.83 (m, 4H), 2.90-2.50 (m, 9H); MS (ESI+) m/z 566 (M+H)+.

Workup

  1. concentrationthe mixture was concentrated
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. stirringAfter stirring for 1 hour
  4. washthe mixture was washed with aqueous 10% K2CO3 (5×25 mL), brine (25 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customThe residue was purified by flash column chromatography on silica gel eluting with (chloroform:methanol, 98:2)

Sources & evidence

ORD record
ord-55f290c14c5d4618ba25fc2fc5969f89
Source dataset
uspto-grants-2014_06
Patent number
US08741938B2

Reaction notes

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