Methanol → HCID 86653603, compound

HRID 1892012Notes

Reaction equation

HRID 1892012 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]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:9][CH:8]=1)(=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:54][OH:55].C(N(CC)CC)C.CN([CH:66]=[O:67])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:26]([O:25][CH:10]1[CH2:11][C:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([C:21]([F:23])([F:22])[F:24])[CH:15]=2)([CH3:13])[C:7]([C:54]([O:67][CH3:66])=[O:55])=[CH:8][CH2:9]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

7

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 86653604HCID 86653604, compound

Product 1

HCID 86653603HCID 86653603, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A solution of (4RS,6RS)-4-(benzyloxy)-6-(4-chloro-3-(trifluoromethyl)phenyl)-6-methylcyclohex-1-enyl trifluoromethanesulfonate (91 mg, 0.172 mmol) in DMF (1 mL) was treated with triphenylphosphine (9 mg, 34 μmol), methanol (279 μl, 6.88 mmol) and triethylamine (48 μl, 344 μmol). The resulting mixture was bubbled with nitrogen for 5 min and then palladium (II) acetate (4 mg, 17 μmol) was added. Upon completion of addition, the resulting solution was bubbled with carbon monoxide for 5 min and then stirred under a carbon monoxide balloon at 70° C. for 23 h. After this time, the mixture was cooled to rt and diluted with ether. The resulting mixture was washed twice with water and once with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under vacuum to yield a residue. The residue was purified by column chromatography on silica gel, eluting with 5-50% ethyl acetate-hexanes, to provide methyl (4RS,6RS)-4-(benzyloxy)-6-(4-chloro-3-(trifluoromethyl)phenyl)-6-methylcyclohex-1-enecarboxylate as a yellow gum (59 mg, 78%). Mass spectrum m/z 456 (M+NH4+), 492 (M+OAc−). 1H NMR (400 MHz, CDCl3) δ 1.68 (s, 3 H) 1.80 (dd, J=12.7, 11.2 Hz, 1 H) 1.98-2.06 (dm, J=12.7 Hz, 1 H) 2.28 (ddd, J=19.0, 9.0, 3.1 Hz, 1 H) 2.65-2.74 (dtd, J=18.8, 5.1, 1.5 Hz, 1 H) 3.28-3.37 (m, 1 H) 3.63 (s, 3 H) 4.32-4.41 (ab, J=11.7 Hz, 2 H) 7.11-7.14 (m, 2 H) 7.16 (dd, J=5.3, 2.8 Hz, 1 H) 7.21-7.28 (m, 3H) 7.32-7.40 (m, 2 H) 7.49 (d, J=2.0 Hz, 1 H).

Workup

  1. customThe resulting mixture was bubbled with nitrogen for 5 min
  2. additionUpon completion of addition
  3. customthe resulting solution was bubbled with carbon monoxide for 5 min
  4. temperatureAfter this time, the mixture was cooled to rt
  5. additiondiluted with ether
  6. washThe resulting mixture was washed twice with water and once with saturated aqueous sodium chloride
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under vacuum
  9. customto yield a residue
  10. customThe residue was purified by column chromatography on silica gel
  11. washeluting with 5-50% ethyl acetate-hexanes

Sources & evidence

ORD record
ord-10f3df8c62984bda8a497ec3509691ff
Source dataset
uspto-grants-2013_08
Patent number
US08507559B2

Reaction notes

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