(Dimethyl sulfide)trihydroboron → 1-(S)-(1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-aminomethylcyclopentane

HRID 1017764Notes

Reaction equation

HRID 1017764 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:20][CH2:19][C@@H:18]([C:21]([NH2:23])=O)[C@@H:17]2[C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.B.CSC>C1COCC1>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:20][CH2:19][C@@H:18]([CH2:21][NH2:23])[C@@H:17]2[C:24]2[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=2)[CH3:14])[CH:4]=[C:3]([C:2]([F:32])([F:1])[F:31])[CH:8]=1

Participants

4

Reactant 2

HCID 12423031(Dimethyl sulfide)trihydroboronHCID 22897428HCID 22897428, compound

Product 1

HCID 228974291-(S)-(1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-aminomethylcyclopentaneYield 51.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 0.70 gm of the amide from Step B in 10 mL of THF was added 2.25 mL of 2M borane-dimethylsulfide in THF. The reaction was stirred at room temperature for 16 hours and then warmed at 50° C. for another 6 hours. The excess borane was quenched with dropwise addition of methanol and then 20 mL of methanol and 5 mL of 2N hydrochloric acid were added and the reaction was stirred at room temperature for 24 hours. The mixture was concentrated in vacuo, diluted with water, made basic with 2N sodium hydroxide and extracted twice with methylene chloride. The organic layers were washed with brine, dried over sodium sulfate, combined and evaporated. The residue was purified by FC (methylene chloride, the 5 -10% methanol in methylene chloride) to give 350 mg of title compound. NMR (CDCl3) δ1.33 (d, 3H, J=6.5 Hz), 1.53 (br s, NH2+H2O), 1.5-1.65 (m, 1H), 1.7-1.85 (m, 1H), 1.85-2.0 (m, 2H), 2.0-2.15 (m, 1H), 2.59 (dd, 1H, J=8 and 10 Hz 2.52 and 2.67 (dABq, 2H, J=4.6 and 12.6 Hz), 3.67 (q, 1H, J=6 Hz), 4.45 (q, 1H, J=6.5 Hz), 6.85-6.95 (m, 2H), 6.95-7.05 (m, 2H), 7.38 (s, 2H), 7.64 (s, 1H). Mass spec (ESI): 450(M+1).

Workup

  1. temperaturewarmed at 50° C. for another 6 hours
  2. customThe excess borane was quenched with dropwise addition of methanol
  3. addition20 mL of methanol and 5 mL of 2N hydrochloric acid were added
  4. stirringthe reaction was stirred at room temperature for 24 hours
  5. concentrationThe mixture was concentrated in vacuo
  6. additiondiluted with water
  7. extractionextracted twice with methylene chloride
  8. washThe organic layers were washed with brine
  9. dry with materialdried over sodium sulfate
  10. customevaporated
  11. customThe residue was purified by FC (methylene chloride

Sources & evidence

ORD record
ord-370a3af0d39545e392d7cf802b19ef5a
Source dataset
uspto-grants-2002_11
Patent number
US06479518B2

Reaction notes

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