Tetrahydrofuran → (1S)-(4-{[5-tert-butoxycarbonylamino-1-(diethoxyphosphoryloxymethyl)-pentyl]isobutyl-sulfamoyl}-phenyl)-carbamic acid tert-butyl ester

HRID 1516425ノート

反応式

HRID 1516425 の反応式
[C:1]([O:5][C:6](=[O:37])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([S:14](=[O:36])(=[O:35])[N:15]([C@H:20]([CH2:33][OH:34])[CH2:21][CH2:22][CH2:23][CH2:24][NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:16][CH:17]([CH3:19])[CH3:18])=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].C1COCC1.[CH2:43]([O:45][P:46](Cl)([O:48][CH2:49][CH3:50])=[O:47])[CH3:44].[H-].[Na+]>C(OP(OCC)(OCC)=O)C>[C:1]([O:5][C:6](=[O:37])[NH:7][C:8]1[CH:9]=[CH:10][C:11]([S:14](=[O:36])(=[O:35])[N:15]([C@H:20]([CH2:33][O:34][P:46]([O:48][CH2:49][CH3:50])([O:45][CH2:43][CH3:44])=[O:47])[CH2:21][CH2:22][CH2:23][CH2:24][NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:16][CH:17]([CH3:18])[CH3:19])=[CH:12][CH:13]=1)([CH3:3])([CH3:4])[CH3:2]

参加物

6

反応物 4

HCID 8028TetrahydrofuranHCID 13139Diethyl chlorophosphateHCID 24758Sodium hydrideHCID 59733922(1S)-{4-[(5-tert-butoxycarbonylamino-1-hydroxymethyl-pentyl)-isobutyl-sulfamoyl]-phenyl}-carbamic acid tert-butyl ester

生成物 1

HCID 59733918(1S)-(4-{[5-tert-butoxycarbonylamino-1-(diethoxyphosphoryloxymethyl)-pentyl]isobutyl-sulfamoyl}-phenyl)-carbamic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 6535Triethyl Phosphate溶媒

実験手順

2.00 g (3.7 mmol) (1S)-{4[(5-tert-butoxycarbonylamino-1-hydroxymethyl-pentyl)-isobutyl-sulfamoyl]-phenyl}-carbamic acid tert-butyl ester (VII) (example 1A, step D) is dissolved in 0.63 mL triethylphosphate and 10 mL THF at 0° C. under inert argon atmosphere. 0.63 mL (4.44 mmol) diethylchlorophosphate is added and then 0.25 g (6.2 mmol), NaH 60% in oil is added in portionwise. The mixture is allowed to warm to room temperature and left to stir for 2 h (LC-MS showed completion after 1 h). To the solution is added 20 mL of Amberlite XAD-2 resin and the slurry thoroughly mixed and added to 200 mL ice water. After stirring for 15 min. the resin suspension is filtered and the resin washed several times with distilled water (500 mL). The desired product is desorbed from the resin with acetone (5×50 mL), EtOAc (5×50 mL), the organic phase is then dried over Na2SO4. After evaporation of the solvent 2.66 g (89%) of clear oil is obtained. The crude product contains a fraction with two diethyl phosphates and is used as is in the next step.

後処理

  1. customat 0° C.
  2. waitleft
  3. additionTo the solution is added 20 mL of Amberlite XAD-2 resin
  4. additionthe slurry thoroughly mixed
  5. stirringAfter stirring for 15 min. the resin suspension
  6. filtrationis filtered
  7. washthe resin washed several times with distilled water (500 mL)
  8. dry with materialthe organic phase is then dried over Na2SO4
  9. customAfter evaporation of the solvent 2.66 g (89%) of clear oil
  10. customis obtained

出典と根拠

ORDレコード
ord-c8946290af384af88dbd91e2735a4442
出典データセット
uspto-grants-2012_07
特許番号
US08227450B2

反応ノート

読み込み中…