Acetic Acid → HCID 86749421, compound

HRID 1720723Notes

Reaction equation

HRID 1720723 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:37]([CH3:39])[CH3:38])=[N:22][C:23]2[C:28]([C:29]=1[C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)=[CH:27][CH:26]=[CH:25][CH:24]=2)([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.CCOCC.CO>[F:36][C:33]1[CH:32]=[CH:31][C:30]([C:29]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]=[C:21]([CH:37]([CH3:39])[CH3:38])[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:35][CH:34]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 9550DiazomethaneHCID 2724141Tetrabutylammonium FluorideHCID 86749422HCID 86749422, compound

Product 1

HCID 86749421HCID 86749421, compoundYield 91%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (S)-3-[[(1,1-Dimethylethyl)diphenylsilyl]oxy]-4-[[[4-(4-fluorophenyl)-2-(1-methylethyl)-3-quinolinyl]ethynyl]methoxyphosphinyl]butanoic acid, methyl ester (1.041 gm, 1.44 mmol), tetra-n-butylammonium fluoride (1.0M in THF, 5.7 ml, 5.7 mmol), and HOAc (525 mg, 8.73 mmol) in THF (14 ml) was stirred at room temperature for 18 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 an oil. The oil was dissolved in cold (0° C.) 1:1 Et2O:MeOH and treated with excess diazomethane for 30 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 actone:hexane) to afford (S)-4-[[[4-(4-Fluorophenyl)-2-(1-methylethyl)-3-quinolinyl]ethynyl]-methoxyphosphinyl]-3-hydroxybutanoic acid, methyl ester (612 mg, 91%) as an 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 an 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 actone:hexane)

Sources & evidence

ORD record
ord-cee344f29b864347b46383c2d4df916a
Source dataset
uspto-grants-1996_04
Patent number
US05506219

Reaction notes

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