Diisopropylethylamine → 2-(trimethylsilyl)ethyl (S)-2-(3-benzoylcyclohexanecarboxamido)-3-cyclohexylpropylmethylcarbamate

HRID 1254239ノート

反応式

HRID 1254239 の反応式
[C:1]([C@@H:9]1[CH2:14][CH2:13][CH2:12][C@H:11]([C:15]([OH:17])=O)[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:18][C@@H:19]([CH2:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)[CH2:20][NH:21][C:22](=[O:30])[O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27].[CH:38](N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C(Cl)Cl.CCOCC.CN(C=O)C>[C:1]([CH:9]1[CH2:14][CH2:13][CH2:12][CH:11]([C:15]([NH:18][C@@H:19]([CH2:31][CH:32]2[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]2)[CH2:20][N:21]([CH3:38])[C:22](=[O:30])[O:23][CH2:24][CH2:25][Si:26]([CH3:28])([CH3:29])[CH3:27])=[O:17])[CH2:10]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11345291rel-(1R,3S)-3-Benzoylcyclohexanecarboxylic acidHCID 59382944(S)-2-(trimethylsilyl)ethyl 2-amino-3-cyclohexylpropylcarbamate

生成物 1

HCID 671917252-(trimethylsilyl)ethyl (S)-2-(3-benzoylcyclohexanecarboxamido)-3-cyclohexylpropylmethylcarbamate収率 94.6%

試薬・触媒・溶媒 3

HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

To a stirred solution of cis-3-benzoylcyclohexane-1-carboxylic acid (78 mg, 0.34 mmol), 2-(trimethylsilyl)ethyl (S)-2-amino-3-cyclohexylpropylcarbamate (116 mg, 0.37 mmol) and diisopropylethylamine (0.13 mL, 0.70 mmol) in CH2Cl2 (2 mL) were added solid 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 200 mg, 0.53 mmol) and DMF (0.5 mL). The mixture was stirred at rt for 3 h, diluted with ether (90 mL), washed with 5% aqueous HCl (25 mL), sat'd aqueous NaHCO3 (25 mL), and brine (25 mL) and dried over Na2SO4. Removal of the solvent under reduced pressure left an oil (260 mg) which was applied to a 2-g silica SPE cartridge and eluted sequentially with 0, 10, 25, 50, 75, and 100% EtOAc in hexanes (15 mL of each) to give six fractions. Fractions 2-4 were pooled and evaporated to afford 2-(trimethylsilyl)ethyl (S)-2-(3-benzoylcyclohexane-carboxamido)-3-cyclohexylpropylmethylcarbamate (170 mg, 91%) as an oil. MS ESI +ve m/z 528 (M+1).

後処理

  1. washwashed with 5% aqueous HCl (25 mL)
  2. dry with materialdried over Na2SO4
  3. customRemoval of the solvent under reduced pressure
  4. waitleft an oil (260 mg) which
  5. washeluted sequentially with 0, 10, 25, 50, 75, and 100% EtOAc in hexanes (15 mL of each)
  6. customto give six fractions
  7. customevaporated

出典と根拠

ORDレコード
ord-6273d671c9b540b094e82e16a227820b
出典データセット
uspto-grants-2013_06
特許番号
US08455521B2

反応ノート

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