Methanol → HCID 9953925, compound

HRID 890357Notes

Reaction equation

HRID 890357 reaction equation
C[CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[C:11]([F:16])[CH:10]=1.B.[CH2:18]1[CH2:22]O[CH2:20][CH2:19]1.CO>C1COCC1>[C:18]1([CH:22]([NH:3][CH2:2][CH2:7][CH:6]2[CH2:7][CH2:2][N:3]([CH2:8][C:9]3[CH:14]=[CH:13][C:12]([F:15])=[C:11]([F:16])[CH:10]=3)[CH2:4][CH2:5]2)[C:11]2[CH:10]=[CH:9][CH:14]=[CH:13][CH:12]=2)[CH:4]=[CH:5][CH:6]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 2723981Borane;tetrahydrofuranHCID 117710745HCID 117710745, compound

Product 1

HCID 9953925HCID 9953925, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the solution of 4-[2-diphenylmethyl)aminocarbonyl]methyl-1-[(3,4-difluorophenyl)methyl]piperidine (0.12 g, 0.28 mmol) in dry THF 20 ml was added 1M BH3/THF (1.0 ml). The reaction solution was refluxed for 6 hours. After the solution was cooled to room temperature, MeOH (5 ml) was added slowly. The solvent was removed under reduced pressure. 10% HCl/MeOH (10 ml) was added into the residue and the solution was refluxed for 1 hour. Solid NaHCO3 was added after MeOH was evaporated. The mixture was extracted with EtOAc. The combined organic phase was dried over Na2SO4 and evaporated to give the crude product, which was purified by chromatography (Hexane/EtOAc/Et3N=1/2/1%) to a white solid, 0.11 g (90% yield) (“Procedure E”). 1H NMR (CD3Cl) δ 7.39-6.99 (13H, m, Ar—H), 4.79 (1H, s, Ph2CH), 3.39 (2H, s, F2PhCH2), 2.80-2.76 (2H, d, J=11.1 Hz, N(CH)2), 2.60-2.55 (2H, t, J=7.0 Hz, NCH2), 1.93-1.86 (2H, t, J=11.1 Hz, N(CH)2), 1.62-1.58 (2H, d, J=12 Hz), 1.49-1.42 (2H, q, J=6.3 Hz, NCH2CH2), 1.35-1.31 (1H, m, NCH2CH2CH(CH2)2), 1.26-1.19 (2H, t, J=12.0 Hz). The free base was converted into its HCl salt, m.p.=280-281° C. Anal: (C27H30N2F2.2HCl.0.25H2O) Calculated: C, 65.12; H, 6.85; N, 5.62; Found: C, 65.13; H, 6.80, N, 5.28.

Workup

  1. temperatureThe reaction solution was refluxed for 6 hours
  2. customThe solvent was removed under reduced pressure
  3. addition10% HCl/MeOH (10 ml) was added into the residue
  4. temperaturethe solution was refluxed for 1 hour
  5. additionSolid NaHCO3 was added after MeOH
  6. customwas evaporated
  7. extractionThe mixture was extracted with EtOAc
  8. dry with materialThe combined organic phase was dried over Na2SO4
  9. customevaporated

Sources & evidence

ORD record
ord-5ced5bc729f849e5a6043d2ac95e51a0
Source dataset
uspto-grants-2006_02
Patent number
US06995268B2

Reaction notes

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