Trifluoroacetic acid methylene chloride → 3'-(((4-(4-Fluorophenyl)piperidin-4-yl)methoxy)methyl)-5'-(trifluoromethyl)biphenyl-4-carbonitrile

HRID 391474Notes

Reaction equation

HRID 391474 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[C:11]([CH2:19][O:20][CH2:21][C:22]3([C:35]4[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=4)[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]3)[CH:10]=2)=[CH:5][CH:4]=1)#[N:2].FC(F)(F)C(O)=O.C(Cl)Cl>>[F:41][C:38]1[CH:37]=[CH:36][C:35]([C:22]2([CH2:21][O:20][CH2:19][C:11]3[CH:10]=[C:9]([C:6]4[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=4)[CH:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=3)[CH2:23][CH2:24][NH:25][CH2:26][CH2:27]2)=[CH:40][CH:39]=1

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 58993637tert-Butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Product 1

HCID 247857163'-(((4-(4-Fluorophenyl)piperidin-4-yl)methoxy)methyl)-5'-(trifluoromethyl)biphenyl-4-carbonitrile

Procedure

tert-Butyl 4-(((4′-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (47.0 mg, 0.09 mmol) was treated with a trifluoroacetic acid/methylene chloride mixture (1:1, 2 mL) 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 removed in vacuo to afford 37.0 mg (92%). 1H-NMR (CDCl3, 500 MHz) δ 7.75 (s, 1H), 7.73 (s, 1H), 7.66 (s, 1H), 7.58 (s, 1H), 7.57 (s, 1H), 7.41 (s, 1H), 7.40 s, 1H), 7.30-7.33 (m, 2H), 6.96-7.00 (m, 2H), 4.46 (s, 2H), 3.44 (s, 2H), 2.87-2.91 (m, 2H), 2.70-2.75 (m, 2H), 2.11-2.14 (m, 2H), 1.87-1.90 (m, 2H). Mass spec.: 469.33 (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 removed in vacuo
  6. customto afford 37.0 mg (92%)

Sources & evidence

ORD record
ord-6fbd0f104e0b47b5aee3d4727cd0352f
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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