Triethyl Phosphate → (1S,5S)-{1-[5-[(4-amino-benzenesulfonyl)-isobutyl-amino]-6-(diethoxy-phosphoryloxy)-hexylcarbamoyl]-2,2-diphenyl-ethyl}-carbamic acid methyl ester

HRID 2041618ノート

反応式

HRID 2041618 の反応式
[CH3:1][O:2][C:3](=[O:44])[NH:4][C@H:5]([C:19](=[O:43])[NH:20][CH2:21][CH2:22][CH2:23][CH2:24][C@H:25]([N:28]([S:33]([C:36]1[CH:41]=[CH:40][C:39]([NH2:42])=[CH:38][CH:37]=1)(=[O:35])=[O:34])[CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:26][OH:27])[CH:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH2:45]([O:47][P:48](OCC)([O:50][CH2:51][CH3:52])=[O:49])[CH3:46].P(Cl)(OCC)(OCC)=O.[H-].[Na+]>O1CCCC1>[CH3:1][O:2][C:3](=[O:44])[NH:4][C@H:5]([C:19](=[O:43])[NH:20][CH2:21][CH2:22][CH2:23][CH2:24][C@H:25]([N:28]([S:33]([C:36]1[CH:41]=[CH:40][C:39]([NH2:42])=[CH:38][CH:37]=1)(=[O:35])=[O:34])[CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:26][O:27][P:48]([O:50][CH2:51][CH3:52])([O:47][CH2:45][CH3:46])=[O:49])[CH:6]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

参加物

6

反応物 4

HCID 6535Triethyl PhosphateHCID 13139Diethyl chlorophosphateHCID 24758Sodium hydrideHCID 513956Ppl-1002 回

生成物 1

HCID 24778259(1S,5S)-{1-[5-[(4-amino-benzenesulfonyl)-isobutyl-amino]-6-(diethoxy-phosphoryloxy)-hexylcarbamoyl]-2,2-diphenyl-ethyl}-carbamic acid methyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

The PL-100 compound (product of step F, 203 mg, 0.325 mmol) was dissolved in dry tetrahydrofuran (3 mL) and 0.2 mL triethylphosphate under N2 atmosphere. The mixture was stirred at this temperature for 15 min, followed by the addition of diethyl chlorophosphate (0.061 mL, 0.423 mmol). Sodium hydride (60% in mineral oil) (17 mg, 0.423 mmol) was added at 0° C. The solution was stirred for 1 h at 0° C. and 12 h at room temperature. 20 mL of Amberlite XAD-2 was added to the solution and the beads were thoroughly mixed with the solvent. To the mixture was added ice water 2 mL, and the THF evaporated off. The beads were then washed with distilled water 6 times 100 mL then extracted three times with ethyl acetate (30 mL). The combined phase was evaporated and the residue was dried under high vacuum. The crude product was purified by flash chromatography using ethyl acetate/hexane (8/2), then EtOAc 100% as eluent. The yield of this reaction is 152 mg 61%.

後処理

  1. stirringThe solution was stirred for 1 h at 0° C. and 12 h at room temperature
  2. addition20 mL of Amberlite XAD-2 was added to the solution
  3. additionthe beads were thoroughly mixed with the solvent
  4. customthe THF evaporated off
  5. washThe beads were then washed with distilled water 6 times 100 mL
  6. extractionthen extracted three times with ethyl acetate (30 mL)
  7. customThe combined phase was evaporated
  8. customthe residue was dried under high vacuum
  9. customThe crude product was purified by flash chromatography

出典と根拠

ORDレコード
ord-61ff812f8ad94dbd97266b9b40bf0786
出典データセット
uspto-grants-2013_11
特許番号
US08580995B2

反応ノート

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