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

HRID 1677218Notes

Reaction equation

HRID 1677218 reaction equation
[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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6535Triethyl PhosphateSolvent

Procedure

2.00 g (3.7 mmol) (1S)-{4-[(5-tert-butoxycarbonylamino-1-hydroxymethyl-pentyl)-isobutyl-sulfamoyl]-phenyl}-carbamic acid tert-butyl ester (VII) (example 1, 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.

Workup

  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

Sources & evidence

ORD record
ord-73c4240d3fe143ebb4ef7ae13df5584e
Source dataset
uspto-grants-2011_08
Patent number
US08008297B2

Reaction notes

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