Trifluoroacetic acid methylene chloride → HCID 24785984, compound

HRID 391478Notes

Reaction equation

HRID 391478 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:16][O:17][CH2:18][C:19]2([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[CH:10][CH:9]=2)[CH:7]=1.FC(F)(F)C(O)=O.C(Cl)Cl>>[Br:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[CH:10][C:11]([C:14]#[N:15])=[CH:12][CH:13]=2)[CH:5]=[C:4]([CH2:16][O:17][CH2:18][C:19]2([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH:3]=1

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 58993705HCID 58993705, compound

Product 1

HCID 24785984HCID 24785984, compound

Procedure

tert-Butyl 4-(((5-bromo-4′-cyanobiphenyl-3-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (24.3 mg, 0.04 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 solvent was evaporated and the compound purified by column chromatography (10% ammonia in methanol/methylene chloride) to afford 13.2 mg (72%). 1H-NMR (CDCl3, 500 MHz) δ 7.71-7.73 (m, 2H), 7.31-7.37 (m, 5H), 7.28 (s, 1H), 7.20-7.22 (m, 2H), 4.38 (s, 2H), 3.44 (s, 2H), 2.91-2.94 (m, 2H), 2.74-2.78 (m, 2H), 2.16-2.20 (m, 2H), 1.89-1.93 (m, 2H). Mass spec.: 463.09 (MH)+. Accurate mass spec.: m/z 463.1205 [MH]+, Δ=1.0 ppm.

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 solvent was evaporated
  6. customthe compound purified by column chromatography (10% ammonia in methanol/methylene chloride)
  7. customto afford 13.2 mg (72%)

Sources & evidence

ORD record
ord-bd7d9bade69a4f15bf62936c8c569c2e
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

Loading…