Ammonium Chloride → (2R)-2-t-Butoxycarbonylamino-1-n-hexanoyloxy-2-methyl-4-(1-methylpyrrol-2-yl)-3-butene

HRID 604547Notes

Reaction equation

HRID 604547 reaction equation
[I-].[CH3:2][N:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[CH2:8][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[K+].[C:34]([O:38][C:39]([NH:41][C@:42]([CH3:54])([CH2:45][O:46][C:47](=[O:53])[CH2:48][CH2:49][CH2:50][CH2:51][CH3:52])[CH2:43]O)=[O:40])([CH3:37])([CH3:36])[CH3:35].[Cl-].[NH4+]>O1CCCC1>[C:34]([O:38][C:39]([NH:41][C@:42]([CH3:43])([CH:54]=[CH:8][C:4]1[N:3]([CH3:2])[CH:7]=[CH:6][CH:5]=1)[CH2:45][O:46][C:47](=[O:53])[CH2:48][CH2:49][CH2:50][CH2:51][CH3:52])=[O:40])([CH3:37])([CH3:36])[CH3:35]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 23031470(1-Methylpyrrol-2-yl)methyltriphenylphosphonium iodideHCID 23665647Potassium tert-butoxideHCID 86614363(2S)-2-t-butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-1-propanol

Product 1

HCID 66672957(2R)-2-t-Butoxycarbonylamino-1-n-hexanoyloxy-2-methyl-4-(1-methylpyrrol-2-yl)-3-buteneYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

(1-Methylpyrrol-2-yl)methyltriphenylphosphonium iodide (58.0 g, 120 mmol) obtained in Reference example 1 (1c) was suspended in tetrahydrofuran (300 mL) and a solution of potassium t-butoxide (13.5 g, 120 mmol) in tetrahydrofuran (180 mL) was added thereto under ice-cooling with stirring over 30 minutes, followed by further stirring of the mixture under ice-cooling for 80 minutes. A solution of (2S)-2-t-butoxycarbonylamino-3-n-hexanoyloxy-2-methyl-1-propanol (30.3 g, 101 mmol) obtained in Reference example 1 (1b) in tetrahydrofuran (120 mL) was added to the reaction mixture over 30 minutes and the mixture was stirred under ice-cooling for 30 minutes. A saturated aqueous ammonium chloride solution was added to the reaction mixture to stop the reaction and the temperature of the liquid was returned to room temperature. The mixture was concentrated under reduced pressure and water and ethyl acetate were added thereto to separate it. The thus obtained organic phase was separated, washed with water and a saturated aqueous NaCl solution and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel chromatography (hexane:ethyl acetate, 9:1) to obtain the title compound (37.0 g, yield: 97%).

Workup

  1. temperatureunder ice-cooling
  2. stirringby further stirring of the mixture under ice-
  3. temperaturecooling for 80 minutes
  4. additionwas added to the reaction mixture over 30 minutes
  5. stirringthe mixture was stirred under ice-
  6. temperaturecooling for 30 minutes
  7. customthe reaction
  8. customwas returned to room temperature
  9. concentrationThe mixture was concentrated under reduced pressure and water and ethyl acetate
  10. additionwere added
  11. customto separate it
  12. customThe thus obtained organic phase was separated
  13. washwashed with water
  14. dry with materiala saturated aqueous NaCl solution and dried over anhydrous sodium sulfate
  15. filtrationAfter filtration
  16. customthe solvent was evaporated under reduced pressure
  17. customthe residue was purified by silica gel chromatography (hexane:ethyl acetate, 9:1)

Sources & evidence

ORD record
ord-f19cdbbf24e7400fa269d1a3b230d35d
Source dataset
uspto-grants-2011_03
Patent number
US07910617B2

Reaction notes

Loading…