Acetic Acid → HCID 86749427, compound

HRID 2295221Notes

Reaction equation

HRID 2295221 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]#[C:15][P:16]([O:25][CH3:26])([CH2:18][CH2:19][CH2:20][C:21]([O:23][CH3:24])=[O:22])=[O:17])=[C:12]([CH:27]([CH3:29])[CH3:28])[CH:11]=[C:10]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[N:9]=2)=[CH:4][CH:3]=1.CC(O)=[O:38].[N+](=C)=[N-]>C1COCC1.CCOCC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]#[C:15][P:16]([O:25][CH3:26])([CH2:18][C@@H:19]([OH:38])[CH2:20][C:21]([O:23][CH3:24])=[O:22])=[O:17])=[C:12]([CH:27]([CH3:28])[CH3:29])[CH:11]=[C:10]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 9550DiazomethaneHCID 86749428HCID 86749428, compound

Product 1

HCID 86749427HCID 86749427, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (S)-3-[[1,1-Dimethylethyl)diphenylsilyl]oxy]-4-[[[2-(4-fluorophenyl)-4-(1-methylethyl)-6-phenyl-3-pyridinyl]ethynyl]methoxyphosphinyl]-butanoic acid, methyl ester (750 mg, 1.00 mmol) tetra-n-butylammonium fluoride (1.0M in THF, 3.50 mmol), and HOAc (330 mg, 5.50 mmol) in THF (12 ml) was stirred at room temperature for 15 hours. The solution was partitioned between 5% KHSO4 and EtOAc. The layers were shaken and separated and the EtOAc layer was washed again with 5% KHSO4. The pooled aqueous washings were back-extracted twice with EtOAc. The combined EtOAc layers were washed with brine and dried (Na2SO4). Filtration and removal the solvent afforded a yellow oil. The oil was dissolved in Et2O 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, 40% acetone in hexane followed by 1:1 acetone:hexane) to afford (S)-4-[[[2-(4-Fluorophenyl)-4-(1-methylethyl)-6-phenyl-3-pyridinyl]ethynyl]methoxyphosphinyl]-3-hydroxybutanoic acid, methyl ester (446 mg, 88%) as a colorless oil.

Workup

  1. customThe solution was partitioned between 5% KHSO4 and EtOAc
  2. stirringThe layers were shaken
  3. customseparated
  4. washthe EtOAc layer was washed again with 5% KHSO4
  5. extractionThe pooled aqueous washings were back-extracted twice with EtOAc
  6. washThe combined EtOAc layers were washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationFiltration and removal the solvent
  9. customafforded a yellow oil
  10. customThe excess diazomethane was destroyed by the addition of HOAc
  11. customthe solvent was removed in vacuo
  12. customThe residue was chromatographed (flash, Merck SiO2, 40% acetone in hexane followed by 1:1 acetone:hexane)

Sources & evidence

ORD record
ord-1ab8d9c8ab1c4589972b31d763fe44ba
Source dataset
uspto-grants-1997_11
Patent number
US05691322

Reaction notes

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