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

HRID 39377ノート

反応式

HRID 39377 の反応式
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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-e109057baab94697b1982b735cdb9eb6
出典データセット
uspto-grants-2013_09
特許番号
US08524753B2

反応ノート

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