Formaldehyde → (+/-)-3'-(1-((1-Methyl-4-phenylpiperidin-4-yl)methoxy)ethyl)-5'-(trifluoromethyl)biphenyl-4-carbonitrile

HRID 391476Notes

Reaction equation

HRID 391476 reaction equation
[C:1]1([C:7]2([CH2:13][O:14][CH:15]([C:17]3[CH:18]=[C:19]([C:27]4[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[CH:29][CH:28]=4)[CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=3)[CH3:16])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:35]([BH3-])#N.[Na+].C=O>C(#N)C>[CH3:35][N:10]1[CH2:11][CH2:12][C:7]([CH2:13][O:14][CH:15]([C:17]2[CH:18]=[C:19]([C:27]3[CH:28]=[CH:29][C:30]([C:33]#[N:34])=[CH:31][CH:32]=3)[CH:20]=[C:21]([C:23]([F:25])([F:26])[F:24])[CH:22]=2)[CH3:16])([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:8][CH2:9]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 24785981(+/-)-3'-(1-((4-Phenylpiperidin-4-yl)methoxy)ethyl)-5'-(trifluoromethyl)biphenyl-4-carbonitrile

Product 1

HCID 24785983(+/-)-3'-(1-((1-Methyl-4-phenylpiperidin-4-yl)methoxy)ethyl)-5'-(trifluoromethyl)biphenyl-4-carbonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of (±)-3′-(1-((4-phenylpiperidin-4-yl)methoxy)ethyl)-5′-(trifluoromethyl)biphenyl-4-carbonitrile (15 mg, 0.032 mmol) and sodium cyanoborohydride (10.2 mg, 0.16 mmol) in acetonitrile (1 mL) at 0° C. was added formalin (0.1 mL, 3.6 mmol). The ice bath was removed and stirring continued for 1 h. The reaction was concentrated and loaded onto an SCX cartridge in methanol. The cartridge was flushed with several volumes of methanol which was discarded. The product was eluted with 2 M ammonia in methanol and concentrated to give 13 mg (84%) as a colorless film. 1H NMR (500 MHz, CDCl3) δ ppm 7.74 (m, 2H), 7.64 (s, 1H), 7.56 (m, 2H), 7.37 (s, 2H), 7.22-7.35 (m, 5H), 7.16 (m, 1H), 4.29 (q, J=6.4 Hz, 1H), 3.32 (d, J=8.9 Hz, 1H), 3.25 (d, J=8.9 Hz, 1H), 2.61 (m, 2H), 2.11-2.35 (m, 7H), 1.95-2.10 (m, 2H), 1.34 (m, 3H). Mass spec.: 479.30 (MH)+. Accurate mass spec.: m/z 479.2300 [MH]+, Δ=2.1 ppm.

Workup

  1. customThe ice bath was removed
  2. concentrationThe reaction was concentrated
  3. customThe cartridge was flushed with several volumes of methanol which
  4. washThe product was eluted with 2 M ammonia in methanol
  5. concentrationconcentrated
  6. customto give 13 mg (84%) as a colorless film

Sources & evidence

ORD record
ord-45c9b796a8514be9850fc3f750733344
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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