Methanol → HCID 86653596, compound

HRID 1892003Notes

Reaction equation

HRID 1892003 reaction equation
FC(F)(F)S(O[C:7]1[C:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([C:21]([F:24])([F:23])[F:22])[CH:15]=2)([CH3:13])[CH2:11][CH:10]([CH2:25][O:26][Si:27]([C:40]([CH3:43])([CH3:42])[CH3:41])([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:9][CH:8]=1)(=O)=O.[CH3:46][OH:47].C(N(CC)C(C)C)(C)C.CN([CH:60]=[O:61])C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Si:27]([O:26][CH2:25][CH:10]1[CH2:11][C:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([C:21]([F:22])([F:24])[F:23])[CH:15]=2)([CH3:13])[C:7]([C:46]([O:61][CH3:60])=[O:47])=[CH:8][CH2:9]1)([C:40]([CH3:42])([CH3:43])[CH3:41])([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 86653597HCID 86653597, compound

Product 1

HCID 86653596HCID 86653596, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
60 °C

Procedure

A solution of (4RS,6RS)-4-((tert-butyldiphenyl-silyloxy)methyl)-6-(4-chloro-3-(trifluoromethyl)phenyl)-6-methylcyclohex-1-enyl trifluoromethane-sulfonate (816 mg, 1.086 mmol) in DMF (4.5 mL) was treated with methanol (1.762 mL, 43.4 mmol) and N,N-diisopropylethylamine (0.569 mL, 3.26 mmol), and bubbled with nitrogen for 5 min. The resulting mixture was treated with dppf (48.2 mg, 0.087 mmol) and palladium (II) acetate (19.51 mg, 0.087 mmol). The resulting solution was bubbled with carbon monoxide for 5 min, and then stirred under a carbon monoxide balloon at 60° C. for 6 h. At the conclusion of this period, the mixture was cooled to rt and diluted with ethyl acetate. The resulting mixture was washed with 1 M aqueous HCl, twice with water, once with saturated aqueous sodium chloride, dried over sodium sulfate and then concentrated under vacuum to yield a residue. The residue was purified by column chromatography on silica gel, eluting with 0-15% ethyl acetate-hexane, to provide methyl (4RS,6RS)-4-((tert-butyldiphenylsilyloxy)-methyl)-6-(4-chloro-3-(trifluoromethyl)phenyl)-6-methyl-cyclohex-1-enecarboxylate as a colorless gum (498 mg, 76%). 1H NMR (400 MHz, CDCl3) δ 7.53 (m, 5 H), 7.36 (m, 7 H), 7.26 (m, 2 H), 3.65 (s, 3 H), 3.43 (d, J=5.3 Hz, 2 H), 2.33 (m, 1 H), 1.98 (ddd, J=19.5, 10.4, 2.4 Hz, 8 H), 1.77 (m, 1 H), 1.62 (s, 3 H), 1.48 (m, 2 H), 0.97 (s, 9 H).

Workup

  1. custombubbled with nitrogen for 5 min
  2. customThe resulting solution was bubbled with carbon monoxide for 5 min
  3. temperatureAt the conclusion of this period, the mixture was cooled to rt
  4. additiondiluted with ethyl acetate
  5. washThe resulting mixture was washed with 1 M aqueous HCl, twice with water, once with saturated aqueous sodium chloride
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customto yield a residue
  9. customThe residue was purified by column chromatography on silica gel
  10. washeluting with 0-15% ethyl acetate-hexane

Sources & evidence

ORD record
ord-7aec51ed1fd845cd8aef655673f9eb92
Source dataset
uspto-grants-2013_08
Patent number
US08507559B2

Reaction notes

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