Formaldehyde → HCID 24785717, compound

HRID 391475Notes

Reaction equation

HRID 391475 reaction equation
[C:1]1([C:7]2([CH2:13][O:14][CH2:15][C:16]3[CH:17]=[C:18]([C:26]4[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][CH:27]=4)[CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=3)[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=O.[C:36]([BH3-])#N.[Na+]>C(#N)C.C(O)(=O)C>[CH3:36][N:10]1[CH2:11][CH2:12][C:7]([CH2:13][O:14][CH2:15][C:16]2[CH:17]=[C:18]([C:26]3[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][CH:27]=3)[CH:19]=[C:20]([C:22]([F:24])([F:25])[F:23])[CH:21]=2)([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:8][CH2:9]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 24785978HCID 24785978, compound

Product 1

HCID 24785717HCID 24785717, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

3′-(((4-Phenylpiperidin-4-yl)methoxy)methyl)-5′-(trifluoromethyl)biphenyl-4-carbonitrile (18.3 mg, 0.04 mmol) and formaldehyde (37 wt. % solution in water, 86.4 μL, 3.22 mmol) were combined in acetonitrile (1.0 mL) and cooled to 0° C. The reaction was treated with sodium cyanoborohydride (12.6 mg, 0.2 mmol) and a few drops of acetic acid. The reaction was stirred at 0° C. for 30 min and at room temperature for 1 h. The solvent was removed in vacuo and the resulting crude mixture passed through a strong cation exchange column. After washing the column with several volumes of methanol, the product was eluted by washing the column with 2 M ammonia in methanol. The solvents were evaporated to afford 12.1 mg (65%). 1H-NMR (CDCl3, 500 MHz) δ 7.74-7.76 (m, 2H), 7.66 (s, 1H), 7.58-7.60 (m, 2H), 7.44 (s, 1H), 7.41 (s, 1H), 7.36-7.38 (m, 2H), 7.30-7.33 (m, 2H), 7.18-7.21 (m, 1H), 4.45 (s, 2H), 3.48 (s, 2H), 2.58-2.60 (m, 2H), 2.17-2.28 (m, 4H), 2.21 (s, 3H), 1.98-2.08 (m, 2H). Mass spec.: 465.11 (MH)+.

Workup

  1. customThe solvent was removed in vacuo
  2. washAfter washing the column with several volumes of methanol
  3. washthe product was eluted
  4. washby washing the column with 2 M ammonia in methanol
  5. customThe solvents were evaporated
  6. customto afford 12.1 mg (65%)

Sources & evidence

ORD record
ord-38d7d8d2d5e241cd91c32507f5b0135f
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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