Acetic Acid → HCID 10950974, compound

HRID 1720716Notes

Reaction equation

HRID 1720716 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]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)=[N:22][C:23]2[C:28]([C:29]=1[CH:30]([CH3:32])[CH3:31])=[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.CCOC(C)=O>[F:39][C:36]1[CH:37]=[CH:38][C:33]([C:21]2[C:20]([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])=[C:29]([CH:30]([CH3:32])[CH3:31])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]=2)=[CH:34][CH:35]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 9550DiazomethaneHCID 2724141Tetrabutylammonium FluorideHCID 86749417HCID 86749417, compound

Product 1

HCID 10950974HCID 10950974, compoundYield 72.4%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (S)-3-[[(1,1-dimethylethyl)diphenylsilyl]oxy]-4-[[[2-(4-fluorophenyl)-4-(1-methylethyl)-3-quinolinyl]ethynyl]methoxyphosphinyl]butanoic acid, methyl ester (729 mg, 0.997 mmol), tetra-n-butylammonium fluoride (1.0M in THF, 3.0 ml, 3.0 mmol), and HOAc (304 mg, 5.06 mmol) in THF (12 ml) was stirred at room temperature for 20 hours. The solution was cooled to 0° C., quenched with 5% KHSO4, and extracted twice with EtOAc. The pooled EtOAc layers were washed twice with 5% KHSO4 and once with brine. The combined aqueous layers were back-extracted 3× with EtOAc and pooled with the initial EtOAc extracts. Drying (Na2SO4), followed by filtration and removal of the solvent afforded a yellow oil. The oil was dissolved in Et2O and EtOAc and treated with excess diazomethane for 30 minutes. The excess diazomethane was destroyed by the addition of HOAc and solvent was removed in vacuo. The residue was chromatographed (flash, Merck SiO2, 40% acetone in hexane) to afford (S)-4-[[[2-(4-fluorophenyl)-4-(1-methylethyl)- 3-quinolinyl]ethynyl]-methoxyphosphinyl]-3-hydroxybutanoic acid, methyl ester (349 mg, 72%) as a white oily foam.

Workup

  1. temperatureThe solution was cooled to 0° C.
  2. customquenched with 5% KHSO4
  3. extractionextracted twice with EtOAc
  4. washThe pooled EtOAc layers were washed twice with 5% KHSO4 and once with brine
  5. extractionThe combined aqueous layers were back-extracted 3× with EtOAc
  6. dry with materialDrying (Na2SO4)
  7. filtrationfollowed by filtration and removal of the solvent
  8. customafforded a yellow oil
  9. customThe excess diazomethane was destroyed by the addition of HOAc and solvent
  10. customwas removed in vacuo
  11. customThe residue was chromatographed (flash, Merck SiO2, 40% acetone in hexane)

Sources & evidence

ORD record
ord-bcd7096fe2624737bf51355e9342bf41
Source dataset
uspto-grants-1996_04
Patent number
US05506219

Reaction notes

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