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Diisopropylethylamine → 4-(2-Benzyloxycarbonylamino-3-methyl-butyryl)-3-phenoxy-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

HRID 1965161
ノート
印刷プレビュー

反応式

HRID 1965161 の反応式
[NH:1]([C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[C@H:2]([C:6]([OH:8])=O)[CH:3]([CH3:5])[CH3:4].[C:19]([O:23][C:24]([N:26]1[CH2:30][CH:29]([O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:28]2[NH:38][CH2:39][CH2:40][CH:27]12)=[O:25])([CH3:22])([CH3:21])[CH3:20].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN1C(=O)CCC1.C(OCC)C.CCOC(C)=O>[C:19]([O:23][C:24]([N:26]1[CH2:30][CH:29]([O:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:28]2[N:38]([C:6](=[O:8])[CH:2]([NH:1][C:9]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:10])[CH:3]([CH3:4])[CH3:5])[CH2:39][CH2:40][CH:27]12)=[O:25])([CH3:22])([CH3:20])[CH3:21]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 726987N-Carbobenzoxy-L-valineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 675137713-Phenoxy-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

生成物 1

HCID 67606394
4-(2-Benzyloxycarbonylamino-3-methyl-butyryl)-3-phenoxy-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester
収率 90.8%

試薬・触媒・溶媒 3

HCID 3283Diethyl Ether溶媒HCID 8857Ethyl Acetate溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
0 °C

実験手順

To a solution containing Cbz-Val-OH (233 mg, 0.92 mmol) and crude 13 (256 mg, 0.84 mmol) in anhydrous NMP (3 mL) was cooled to 0° C. HATU (352 mg, 0.93 mmol) and DIPEA (125 mg, 1.01 mmol) were added and the reaction mixture was slowly warmed to ambient temperature. After 16 h, the reaction mixture was diluted with diethyl ether and EtOAc (1:4) and washed successively with 1M HCl, aqueous NaHCO3, water, and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by flash silica gel chromatography (4:1 hexanes/EtOAc) to afford 410 mg (90%) of 14 as a white solid. 1H NMR (CDCl3, 300 MHz), mixture of rotomers: δ7.31 (m, 9H), 6.96 (m, 1H), 5.79 (m, 1H). 5.07 (m, 2H), 4.91 (d, J=2.7 Hz, 1H), 4.51-4.43 (m, 2H), 4.35 (t, J=7.5 Hz, 1H), 4.07-3.99 (m, 2H), 3.90 (app d, J=26.4 Hz, 0.5H), 3.77 (app d, J=27.3 Hz, 0.5H), 3.31 (m, 2H), 2.49 (m, 0.5H), 2.35 (m, 0.5H), 1.92 (m, 1H), 1.51 (m, 9H), 0.95 (m, 6H) ppm.

後処理

  1. temperaturethe reaction mixture was slowly warmed to ambient temperature
  2. washwashed successively with 1M HCl, aqueous NaHCO3, water, and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by flash silica gel chromatography (4:1 hexanes/EtOAc)

出典と根拠

ORDレコード
ord-567e39736ad2456ba7a415d72fa5e3d7
出典データセット
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08415486B2

反応ノート

読み込み中…

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