Boron trifluoride etherate → HCID 86620044, compound

HRID 1993975Notes

Reaction equation

HRID 1993975 reaction equation
[N+](C1C=CC(C(O[CH:11]2[CH:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH:15]([CH2:24][O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:14]([CH2:33][O:34][C:35](=[O:45])[C:36]3[CH:41]=[CH:40][C:39]([N+:42]([O-:44])=[O:43])=[CH:38][CH:37]=3)[CH2:13][O:12]2)=O)=CC=1)([O-])=O.[F:48][C:49]([F:64])([F:63])[C:50]1[CH:51]=[C:52]([C@H:60]([OH:62])[CH3:61])[CH:53]=[C:54]([C:56]([F:59])([F:58])[F:57])[CH:55]=1.B(F)(F)F.CCOCC>C(Cl)Cl>[N+:42]([C:39]1[CH:38]=[CH:37][C:36]([C:35]([O:34][CH2:33][C@@H:14]2[C@@H:15]([CH2:24][O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C@H:16]([C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[C@@H:11]([O:62][C@@H:60]([C:52]3[CH:51]=[C:50]([C:49]([F:63])([F:64])[F:48])[CH:55]=[C:54]([C:56]([F:57])([F:58])[F:59])[CH:53]=3)[CH3:61])[O:12][CH2:13]2)=[O:45])=[CH:41][CH:40]=1)([O-:44])=[O:43]

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 2779031(alphaR)-alpha-Methyl-3,5-bis(trifluoromethyl)benzenemethanolHCID 86620045HCID 86620045, compound

Product 1

HCID 86620044HCID 86620044, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-25 °C

Procedure

The intermediate from example 1 step G (10.95 g, 17.0 mmol) was combined with (1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethanol (4.39 g, 17.0 mmol) and dissolved in 170 mL DCM. The vessel was cooled to −25° C. followed by the addition boron trifluoride etherate (0.48 g, 3.4 mmol). The reaction vessel was maintained at −25° C. for 1 hr. The reaction was quenched by the addition of a saturated solution of NaHCO3 and the mixture was allowed to warm to ambient temperature. The aqueous mixture was extracted several times with EtOAc and washed with brine, dried over Na2SO4, filtered through a fritted funnel and concentrated in vacuo. The crude residue was purified on silica gel and eluted toluene. The first component collected off the column was the unwanted diastereomer. The second component collected was the desired diastereomer and was determined to be 85% pure as determined by 1HNMR. The product was recrystallized from cold methanol to provide the pure title compound. 1H-NMR (CDCl3): δ 1.41 (d, 3H, J=6.5 Hz), 1.76-1.84 (m, 1H), 2.50-2.62 (m, 1H), 3.02 (dd, 1H, J=9.0, 12.0 Hz), 3.07 (dd, 1H, J=3.0, 9.5 Hz), 3.41 (dd, 1H, J=2.5, 10.0 Hz), 3.54 (dd, 1H, J=11.5, 11.5 Hz), 4.26-4.36 (m, 5H), 4.56 (dd, 1H, J=3.5, 11.0 Hz), 4.99 (q, 1H, J=6.5 Hz), 6.92-7.06 (m, 4H), 7.20-7.36 (m, 7H), 7.71 (s, 1H), 8.19 (d, 2H, J=9.0 Hz), 8.31 (d, 2H, J=9.0 Hz) ppm.

Workup

  1. temperatureThe reaction vessel was maintained at −25° C. for 1 hr
  2. customThe reaction was quenched by the addition of a saturated solution of NaHCO3
  3. temperatureto warm to ambient temperature
  4. extractionThe aqueous mixture was extracted several times with EtOAc
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered through a fritted funnel
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified on silica gel
  10. washeluted toluene
  11. customThe first component collected off the column
  12. customThe second component collected
  13. customThe product was recrystallized from cold methanol

Sources & evidence

ORD record
ord-904ab9034cd342b4aeff71a3d08186d2
Source dataset
uspto-grants-2010_01
Patent number
US07652058B2

Reaction notes

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