Diisopropylethylamine → Carbamic acid, [(1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(cyclohexyloxy)amino]-2-hydroxy-1-(phenylmethyl)propyl]-, (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester

HRID 1166507

反応式

HRID 1166507 の反応式
[CH2:1]([C@H:8]([NH:20][C:21](=[O:31])[O:22][C@@H:23]1[C@H:30]2[C@H:26]([O:27][CH2:28][CH2:29]2)[O:25][CH2:24]1)[C@H:9]([OH:19])[CH2:10][NH:11][O:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:32]1[C:36]2[CH:37]=[CH:38][C:39]([S:41](Cl)(=[O:43])=[O:42])=[CH:40][C:35]=2[O:34][CH2:33]1.C(N(C(C)C)CC)(C)C>O1CCCC1.CN(C1C=CC=CN=1)C>[O:32]1[C:36]2[CH:37]=[CH:38][C:39]([S:41]([N:11]([O:12][CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]3)[CH2:10][C@@H:9]([OH:19])[C@@H:8]([NH:20][C:21](=[O:31])[O:22][C@@H:23]3[C@H:30]4[C@H:26]([O:27][CH2:28][CH2:29]4)[O:25][CH2:24]3)[CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)(=[O:42])=[O:43])=[CH:40][C:35]=2[O:34][CH2:33]1

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 49134011,3-Benzodioxole-5-sulfonyl chloride2 回HCID 59090777(3r,3As,6ar)hexahydrofuro[2,3-b]furan-3-yl(1s,2r)-1-benzyl-3-[(cyclohexyloxy)amino]-2-hydroxypropylcarbamate

生成物 1

HCID 6321056Carbamic acid, [(1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(cyclohexyloxy)amino]-2-hydroxy-1-(phenylmethyl)propyl]-, (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester収率 87%

試薬・触媒・溶媒 2

HCID 218852-Dimethylaminopyridine触媒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-[(cyclohexyloxy)amino]-2-hydroxypropylcarbamate (100 mg, 0.230), 1,3-benzodioxole-5-sulfonyl chloride (Eur. Pat. Appl. 583960, Feb 23, 1994, 56 mg, 0.253 mmol) and diisoproylethylamine (0.042 mL, 0.242 mmol) in anhydrous tetrahydrofuran (3 mL) was stirred at ambient temperature under an Argon atmosphere for 16 hours. A catalytic quantity of dimethylaminopyridine (˜1 mg) was added and the reaction was heated at reflux for approximately 2 hours. An additional quantity of 1,3-benzodioxole-5-sulfonyl chloride (11 mg, 0.050 mmol) was added and the reaction was heated for an additional hour. After cooling to ambient temperature, the reaction mixture was partitioned between ethyl acetate and aqueous hydrochloric acid. After separating the phases, the organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The residue was purified on a preparative TLC plate (20×20 cm, 500 μM) eluting with 1:1 ethyl acetate:hexane. The product band was removed, eluted with 3:1 methylene chloride : methanol, filtered, and evaporated in vacuo. The residue was triturated with water, filtered and dried under high vacuum to provide (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(cyclohexyloxy)amino]-1-benzyl-2-hydroxypropylcarbamate (123 mg, 87%) as a white solid. H1-NMR (chloroform-D3): 1.32 (m, 6H), 1.70 (m, 5H), 2.14 (m, 2H), 3.00 (m, 4H), 3.18 (b, 1H), 3.74 (m, 2H), 3.97 (m, 4H), 4.27 (m, 1H), 4.90 (m, 1H), 5.07 (m, 1H), 5.70 (d, 1H), 6.15 (s, 2H), 6.95 (d, 1H), 7.30 (m, 7H). MS(ESI): 641(M+Na).

後処理

  1. temperaturethe reaction was heated
  2. temperatureat reflux for approximately 2 hours
  3. temperaturethe reaction was heated for an additional hour
  4. temperatureAfter cooling to ambient temperature
  5. customthe reaction mixture was partitioned between ethyl acetate and aqueous hydrochloric acid
  6. customAfter separating the phases
  7. washthe organic layer was washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe residue was purified on a preparative TLC plate (20×20 cm, 500 μM)
  12. washeluting with 1:1 ethyl acetate
  13. customThe product band was removed
  14. washeluted with 3:1 methylene chloride
  15. filtrationmethanol, filtered
  16. customevaporated in vacuo
  17. customThe residue was triturated with water
  18. filtrationfiltered
  19. customdried under high vacuum

出典と根拠

ORDレコード
ord-ab899be85d3d4abea60cc4df7e6f255c
出典データセット
uspto-grants-2003_09
特許番号
US06613743B2

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