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Diisopropylethylamine → (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[([4-(benzyloxy)phenyl]sulfonyl}(1-ethylpropoxy)amino]-2-hydroxypropylcarbamate

HRID 29217
ノート
印刷プレビュー

反応式

HRID 29217 の反応式
[CH2:1]([C@H:8]([NH:19][C:20](=[O:30])[O:21][C@@H:22]1[C@H:29]2[C@H:25]([O:26][CH2:27][CH2:28]2)[O:24][CH2:23]1)[C@H:9]([OH:18])[CH2:10][NH:11][O:12][CH:13]([CH2:16][CH3:17])[CH2:14][CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:31]([O:38][C:39]1[CH:44]=[CH:43][C:42]([S:45](Cl)(=[O:47])=[O:46])=[CH:41][CH:40]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(N(C(C)C)CC)(C)C>O1CCCC1.CN(C1C=CC=CN=1)C>[CH2:1]([C@H:8]([NH:19][C:20](=[O:30])[O:21][C@@H:22]1[C@H:29]2[C@H:25]([O:26][CH2:27][CH2:28]2)[O:24][CH2:23]1)[C@H:9]([OH:18])[CH2:10][N:11]([S:45]([C:42]1[CH:41]=[CH:40][C:39]([O:38][CH2:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)=[CH:44][CH:43]=1)(=[O:47])=[O:46])[O:12][CH:13]([CH2:14][CH3:15])[CH2:16][CH3:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 47383854-(Benzyloxy)benzene-1-sulfonyl chlorideHCID 59090756(3R,3aS, 6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[(l-ethylpropoxy)amino]-2-hydroxypropylcarbamate

生成物 1

HCID 59090701(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[([4-(benzyloxy)phenyl]sulfonyl}(1-ethylpropoxy)amino]-2-hydroxypropylcarbamate収率 74.1%

試薬・触媒・溶媒 2

HCID 218852-Dimethylaminopyridine触媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[(1-ethylpropoxy)amino]-2-hydroxypropylcarbamate (200 mg, 0.474 mmol), 4-benzyloxybenzenesulphonyl chloride (134 mg, 0.474 mmol), diisoproylethylamine (0.083 mL, 0.474 mmol) and dimethylaminopyridine (˜1 mg) in anhydrous tetrahydrofuran (3 mL) was stirred at ambient temperature over 16 hours under an Argon atmosphere. The reaction mixture was warmed to 55° C. and an additional quantity of dimethylaminopyridine (˜2 mg) was added. After stirring for 2 hours, the reaction was evaporated in vacuo and the residue was partitioned between dichloromethane and aqueous sodium hydrogen sulfate (1N). After separating the phases, the aqueous layer was extracted with dichloromethane. The combined organic phases were dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The residue was purified on flash grade silica gel eluting with 3:2 ethyl acetate:hexane. Fractions containing the product were combined, evaporated in vacuo, and dried under high vacuum to provide (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-3-[{[4-(benzyloxy)phenyl]sulfonyl}(1-ethylpropoxy)amino]-2-hydroxypropylcarbamate (235 mg, 74%) as a foam. H1-NMR (chloroform-D3): 0.94 (m, 6H), 1.62 (m, 7H), 3.05 (m, 5H), 3.74 (m, 2H), 3.98 (m, 4H), 4.18 (m, 1H), 4.88 (d, 1H), 5.08 (m, 1H), 5.19 (s, 2H), 5.70 (d, 1H), 7.13 (d, 2H), 7.34 (m, 10H), 7.80 (d, 2H). MS(ESI): 691(M+Na).

後処理

  1. temperatureThe reaction mixture was warmed to 55° C.
  2. stirringAfter stirring for 2 hours
  3. customthe reaction was evaporated in vacuo
  4. customthe residue was partitioned between dichloromethane and aqueous sodium hydrogen sulfate (1N)
  5. customAfter separating the phases
  6. extractionthe aqueous layer was extracted with dichloromethane
  7. dry with materialThe combined organic phases were dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe residue was purified on flash grade silica gel eluting with 3:2 ethyl acetate
  11. additionFractions containing the product
  12. customevaporated in vacuo
  13. customdried under high vacuum

出典と根拠

ORDレコード
ord-a8cce7836032403e80e046db7d969d22
出典データセット
uspto-grants-2008_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07419967B2

反応ノート

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