Tetrafluoroboric acid → HCID 42639483, compound

HRID 1393321Notes

Reaction equation

HRID 1393321 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[C@@H:13]([OH:14])[CH2:12][CH2:11][C@H:10]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C@H:9]2[C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:4][CH:3]=1.[F:25][C:26]([F:47])([F:46])[C:27]1[CH:28]=[C:29]([C@@H:37](OC(=N)C(Cl)(Cl)Cl)[CH3:38])[CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1.[H+].[B-](F)(F)(F)F>CCOCC>[F:25][C:26]([F:46])([F:47])[C:27]1[CH:28]=[C:29]([C@H:37]([O:14][C@H:13]2[CH2:12][CH2:11][C@H:10]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C@@H:9]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[C@@H:8]2[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH3:38])[CH:30]=[C:31]([C:33]([F:34])([F:35])[F:36])[CH:32]=1

Participants

5

Reactant 3

HCID 28118Tetrafluoroboric acidHCID 11611082Trichloroacetimidic acid (S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl esterHCID 42639482(1S,2S,3R,4S)-diethyl 3-(4-fluorophenyl)-4-hydroxycyclohexane-1,2-dicarboxylate

Product 1

HCID 42639483HCID 42639483, compoundYield 59.1%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 9.09 g (26.9 mmol) of the first eluting isomer diethyl(1S,2S,3R,4S)-3-(4-fluorophenyl)-4-hydroxycyclohexane-1,2-dicarboxylate (step D) and 21.5 g (53.5 mmol) of (1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl-2,2,2-trichloroethanimidoate (step E) in 250 mL of cyclohexane/1,2-chloroethane (3/1) under nitrogen atmosphere at −5° C. was added 0.51 mL (3.58 mmol) of 54% HBF4 in ether. The reaction mixture was stirred at −5° C. to at 0° C. for 2 hr then diluted with ether. The mixture was washed with sat. aq. NaHCO3. The organic layer was dried over drying agent, filtered and the solvent evaporated under vacuum. The residue was purified by flash column chromatography on silica gel eluting with EtOAc/hexanes (1/4) to give 9.2 g of the title compound as an oil. 1H-NMR (CDCl3): δ: δ: 7.70 (1 H, s), 7.20 (2 H, s), 7.00 (2 H, m), 6.85 (2 H, t, J=8.5 Hz), 4.43 (1 H, q, J=6.0 Hz), 4.20-4.10 (2 H, m), 3.80-3.73 (2 H, m), 3.36 (1 H, m), 2.90-2.76 (2 H, m), 2.40 (1 H, m), 2.28 (1 H, m), 1.63-1.55 (2 H, m), 1.33 (3 H, d, J=6.0 Hz), 1.25 (3 H, t, J=7.2 Hz), 0.82 (3 H, t, J=7.2 Hz). Unreacted starting alcohol could be recovered by flushing the column with EtOAc and reused in the above reaction.

Workup

  1. washThe mixture was washed with sat. aq. NaHCO3
  2. customThe organic layer was dried
  3. customover drying agent
  4. filtrationfiltered
  5. customthe solvent evaporated under vacuum
  6. customThe residue was purified by flash column chromatography on silica gel eluting with EtOAc/hexanes (1/4)

Sources & evidence

ORD record
ord-e0611fbf4e3545bc8101d4b27bc1b800
Source dataset
uspto-grants-2008_03
Patent number
US07345083B2

Reaction notes

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