Acetic Acid → HCID 86746697, compound

HRID 1590081Notes

Reaction equation

HRID 1590081 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[C:31]([C:32]#[C:33][P:34]([O:61][CH3:62])([CH2:36][C@@H:37]([O:43][Si](C(C)(C)C)(C3C=CC=CC=3)C3C=CC=CC=3)[CH2:38][C:39]([O:41][CH3:42])=[O:40])=[O:35])=[C:30]([CH:63]([CH3:65])[CH3:64])[N:29]=[C:28]([C:66]3[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=3)[N:27]=2)=[CH:22][CH:21]=1.C(O)(=O)C>C1COCC1.CCOCC.CCOC(C)=O>[F:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]2[C:31]([C:32]#[C:33][P:34]([O:61][CH3:62])([CH2:36][C@@H:37]([OH:43])[CH2:38][C:39]([O:41][CH3:42])=[O:40])=[O:35])=[C:30]([CH:63]([CH3:65])[CH3:64])[N:29]=[C:28]([C:66]3[CH:67]=[CH:68][CH:69]=[CH:70][CH:71]=3)[N:27]=2)=[CH:24][CH:25]=1

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 2724141Tetrabutylammonium FluorideHCID 86746696HCID 86746696, compound

Product 1

HCID 86746697HCID 86746697, compoundYield 64%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Tetrabutylammonium fluoride ((Bu)4NF) (1.0M in THF, 2.91 ml, 2.91 mmol) was added to a mixture of (S)-4-[[[4-(4-fluorophenyl)-6-(1-methylethyl)-2-phenyl-5-pyrimidinyl]-ethynyl]-methoxyphosphinyl]-3-((t-butyl)diphenylsilyloxy)-butanoic acid, methyl ester obtained in step (vi) above (0.709 gm, 0.97 mmol) and acetic acid (0.233 gm, 3.89 mmol) in THF (10 ml). The solution was allowed to stir for 20 hours at room temperature. The solution was diluted with ether and then washed with 5% KHSO4 (3x). The aqueous layers were back-extracted with EtOAc (3x). The organic layers were pooled and washed with brine, then dried over Na2SO4, filtered and concentrated to afford a yellow gum. The gum was redissolved in EtOAc, then washed with saturated NaHCO3, 5% KHSO4 and brine, then dried over Na2SO4 filtered and concentrated to a yellow oil. The oil was dissolved in methanol (15 ml) at 0° C. and treated with CH2N2. Excess CH2N2 was removed in a stream of argon, and the solution was concentrated to a yellow oil. The oil was purified by flash chromatography on Merck silica gel in 40% acetone in hexane. The desired fractions were pooled and concentrated to afford the title compound as a clear oil (0.315 gm, 64%). TLC: Rf =0.49 (50% acetone in hexane).

Workup

  1. washwashed with 5% KHSO4 (3x)
  2. extractionThe aqueous layers were back-extracted with EtOAc (3x)
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a yellow gum
  8. washwashed with saturated NaHCO3, 5% KHSO4 and brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to a yellow oil
  12. dissolutionThe oil was dissolved in methanol (15 ml) at 0° C.
  13. additiontreated with CH2N2
  14. customExcess CH2N2 was removed in a stream of argon
  15. concentrationthe solution was concentrated to a yellow oil
  16. customThe oil was purified by flash chromatography on Merck silica gel in 40% acetone in hexane
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-7aac9190e2dd42bfa114f3ee80c21dd1
Source dataset
uspto-grants-1993_04
Patent number
US05202327

Reaction notes

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