Triethylamine → Ethyl(1S,2R,3S,6S)-3-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-2-(4-fluorophenyl)-6-formylcyclohexanecarboxylate

HRID 2245248Notes

Reaction equation

HRID 2245248 reaction equation
C(Cl)(=O)C(Cl)=O.[F:7][C:8]([F:43])([F:42])[C:9]1[CH:10]=[C:11]([C@H:19]([O:21][C@H:22]2[CH2:27][CH2:26][C@H:25]([CH2:28][OH:29])[C@@H:24]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[C@@H:23]2[C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=2)[CH3:20])[CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1.C(N(CC)CC)C>ClCCl>[F:42][C:8]([F:7])([F:43])[C:9]1[CH:10]=[C:11]([C@H:19]([O:21][C@H:22]2[CH2:27][CH2:26][C@H:25]([CH:28]=[O:29])[C@@H:24]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[C@@H:23]2[C:35]2[CH:36]=[CH:37][C:38]([F:41])=[CH:39][CH:40]=2)[CH3:20])[CH:12]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:14]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 86628112Ethyl(1R,2R,3S,6S)-3-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-2-(4-fluorophenyl)-6-(hydroxymethyl)cyclohexanecarboxylate

Product 1

HCID 86628113Ethyl(1S,2R,3S,6S)-3-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-2-(4-fluorophenyl)-6-formylcyclohexanecarboxylateYield 9.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of oxalyl chloride (0.22 mL, 2.6 mmol) in 40 mL dichloromethane was slowly added under nitrogen DMSO (0.13 mL, 1.8 mmol) at −78° C. The mixture was stirred for 5 min at the same temperature. Intermediate alcohol obtained from Step B (0.46 g, 8.6 mmol) in 15 mL dichloromethane was added by injection. Stirring continued at −78° C. for 20 min. Triethylamine (0.48 mL, 3.4 mmol) was added. The cooling bath was removed and the mixture was stirred until the temperature rose to −0° C. The reaction was quenched with sat. aq. NH4Cl. The organic layer was separated and the aqueous was extracted with dichloromethane (40 mL×2). The combined organic extracts were washed with brine, dried over MgSO4, filtered and the solvent was removed under vacuum to give 0.45 g title compound which was used without further purification. 1H-NMR (CDCl3): δ: 9.64 (1H, s), 7.71 (1H, s), 7.22 (2H, s), 7.00 (2H, m), 6.86 (2H, m), 4.43 (1H, q, J=6.4 Hz), 3.80 (2H, q, J=7.1 Hz), 3.34 (1H, m), 2.84 (2H, m), 2.66 (1H, m), 2.46 (1H, m), 2.32 (1H, m), 1.64 (2H, m), 1.42 (1H, m), 1.35 (3H, d, J=6.4 Hz), 0.82 (3H, t, J=7.1 Hz).

Workup

  1. stirringStirring
  2. waitcontinued at −78° C. for 20 min
  3. customThe cooling bath was removed
  4. stirringthe mixture was stirred until the temperature
  5. customrose to −0° C
  6. customThe reaction was quenched with sat. aq. NH4Cl
  7. customThe organic layer was separated
  8. extractionthe aqueous was extracted with dichloromethane (40 mL×2)
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-1eb7b10e06a64d00b3ad6f2029edb5b3
Source dataset
uspto-grants-2010_03
Patent number
US07683068B2

Reaction notes

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