Acetic Acid → HCID 86749414, compound

HRID 1720711Notes

Reaction equation

HRID 1720711 reaction equation
CC([Si](C1C=CC=CC=1)(C1C=CC=CC=1)[O:6][C@H:7]([CH2:13][P:14]([C:18]#[C:19][C:20]1[C:21]([CH:39]([CH3:41])[CH3:40])=[N:22][C:23]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:24][C:25]=1[C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)([O:16][CH3:17])=[O:15])[CH2:8][C:9]([O:11][CH3:12])=[O:10])(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CC(O)=O.[N+](=C)=[N-]>C1COCC1.O.CCOCC>[F:32][C:29]1[CH:30]=[CH:31][C:26]([C:25]2[CH:24]=[C:23]([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)[N:22]=[C:21]([CH:39]([CH3:40])[CH3:41])[C:20]=2[C:19]#[C:18][P:14]([O:16][CH3:17])([CH2:13][C@@H:7]([OH:6])[CH2:8][C:9]([O:11][CH3:12])=[O:10])=[O:15])=[CH:27][CH:28]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 9550DiazomethaneHCID 2724141Tetrabutylammonium FluorideHCID 86749415HCID 86749415, compound

Product 1

HCID 86749414HCID 86749414, compoundYield 85%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (S)-3-[[(1,1-dimethylethyl)diphenylsilyl]oxy]-4-[[[4-(4-fluorophenyl)-2-(1-methylethyl)-6-phenyl-3-pyridinyl]ethynyl]methoxyphosphinyl]butanoic acid, methyl ester (800 mg, 1.07 mmol), tetra-n-butylammonium fluoride (1.0M in THF, 3.21 ml, 3.21 mmol), and HOAc (325 mg, 5.41 mmol) in THF (12 ml) was stirred at room temperature for 17 hours. The solution was cooled to 0° C., diluted with H2O, and extracted twice with EtOAc. The pooled EtOAc layers were washed with saturated NaHCO3 and brine. The organic layer was then washed twice 5% KHSO4, then with H2O and brine. Drying (Na2SO4), followed by filtration and removal of the solvent afforded a yellow oil. The oil was dissolved in Et2O (10 ml) and treated with excess diazomethane for 20 minutes. The excess diazomethane was destroyed by the addition of HOAc and the solvent was removed in vacuo. The residue was chromatographed (flash, Merck SiO2, 50×70 mm column 35% acetone in hexane (650 ml) followed by 1:1 acetone:hexane) to afford (S)-4-[[[4-(4-fluorophenyl)-2-(1-methylethyl)-6-phenyl-3-pyridinyl]-ethynyl]methoxyphosphinyl]-3-hydroxybutanoic acid, methyl ester (463 mg, 85%) as a colorless foam.

Workup

  1. temperatureThe solution was cooled to 0° C.
  2. extractionextracted twice with EtOAc
  3. washThe pooled EtOAc layers were washed with saturated NaHCO3 and brine
  4. washThe organic layer was then washed twice 5% KHSO4
  5. dry with materialDrying (Na2SO4)
  6. filtrationfollowed by filtration and removal of the solvent
  7. customafforded a yellow oil
  8. customThe excess diazomethane was destroyed by the addition of HOAc
  9. customthe solvent was removed in vacuo
  10. customThe residue was chromatographed (flash, Merck SiO2, 50×70 mm column 35% acetone in hexane (650 ml) followed by 1:1 acetone:hexane)

Sources & evidence

ORD record
ord-5331fa3dfaa544e398e87427824dc614
Source dataset
uspto-grants-1996_04
Patent number
US05506219

Reaction notes

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