Acetic Acid → HCID 24801107, compound

HRID 656521Notes

Reaction equation

HRID 656521 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([CH:18]([O:20][CH2:21][C:22]3([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[CH3:19])[N:9]=2)=[CH:4][CH:3]=1.C=O.[C:36](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([F:17])([F:15])[F:16])[CH:11]=[C:10]([CH:18]([O:20][CH2:21][C:22]3([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH2:27][CH2:26][N:25]([CH3:36])[CH2:24][CH2:23]3)[CH3:19])[N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 68879582HCID 68879582, compound

Product 1

HCID 24801107HCID 24801107, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2-(4-fluorophenyl)-6-(1-((4-phenylpiperidin-4-yl)methoxy)ethyl)-4-(trifluoromethyl)pyridine (40 mg, 0.08 mmol), and formaldehyde (37 wt. % solution in water, 0.2 mL, 7.5 mmol) were combined in dichloromethane (2.0 mL) and cooled to 0° C. The reaction was treated with sodium triacetoxyborohydride (74 mg, 0.3 mmol) and a drop 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 was concentrated and purified by preparative HPLC which afforded 10.0 mg (27%) 1H-NMR (CD3OD, 400 MHz) δ 8.09 (m, 1H), 7.93 (m, 1H), 7.14-7.58 (m, 9H), 4.51 (q, 1H), 3.36-3.52 (m, 2H), 2.80-2.93 (m, 2H), 2.59-2.79 (m, 5H), 2.04-2.24 (m, 2H), 1.42 (d, 3H), LC: Tr=1.952 min HPLC Method 1. Mass spec.: 473.36 (MH)+.

Workup

  1. customThe solvent was removed in vacuo
  2. concentrationthe resulting crude mixture was concentrated
  3. custompurified by preparative HPLC which
  4. customafforded 10.0 mg (27%) 1H-NMR (CD3OD, 400 MHz) δ 8.09 (m, 1H), 7.93 (m, 1H), 7.14-7.58 (m, 9H), 4.51 (q, 1H), 3.36-3.52 (m, 2H), 2.80-2.93 (m, 2H), 2.59-2.79 (m, 5H), 2.04-2.24 (m, 2H), 1.42 (d, 3H), LC
  5. customTr=1.952 min HPLC Method 1

Sources & evidence

ORD record
ord-4a4d01d5f32c464186d49f07ce06b99a
Source dataset
uspto-grants-2011_12
Patent number
US08071778B2

Reaction notes

Loading…