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

HRID 39377Notes

Reaction equation

HRID 39377 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-e109057baab94697b1982b735cdb9eb6
Source dataset
uspto-grants-2013_09
Patent number
US08524753B2

Reaction notes

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