Acetyl chloride → 1-Acetyl-4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]piperidine-4-carbonitrile

HRID 273025Notes

Reaction equation

HRID 273025 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[N:5]1([CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3([C:26]#[N:27])[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)=[CH:16][CH:15]=2)[CH2:9][CH2:8][CH2:7][CH2:6]1.C(N(CC)CC)C>ClCCl>[C:1]([N:23]1[CH2:22][CH2:21][C:20]([C:17]2[CH:18]=[CH:19][C:14]([O:13][CH2:12][CH2:11][CH2:10][N:5]3[CH2:9][CH2:8][CH2:7][CH2:6]3)=[CH:15][CH:16]=2)([C:26]#[N:27])[CH2:25][CH2:24]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 598373684-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]piperidine-4-carbonitrile

Product 1

HCID 598375201-Acetyl-4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]piperidine-4-carbonitrileYield 28.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Acetyl chloride (27 μl, 0.37 mmol) was added dropwise to a solution of 4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]piperidine-4-carbonitrile (90 mg, 0.28 mmol) and triethylamine (78 μl, 0.56 mmol) in dichloromethane (3 ml). The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with dichloromethane (15 ml) and washed with water (15 ml). The layers were separated and the aqueous layer was further extracted with dichloromethane (2×10 ml). The organics were combined, washed with brine, dried over sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with ethyl acetate:methanol:ammonia (95:5:0.5 by volume) to provide the title compound (28 mg, 28%). 1H NMR (400 MHz, CD3OD) δ 1.82-1.85 (m, 4H), 1.89-2.18 (m, 9H), 2.60-2.63 (m, 4H), 2.69 (t, 2H), 3.00 (t, 1H), 3.50 (t, 1H), 4.03-4.12 (m, 3H), 4.70 (d, 1H), 6.97 (d, 2H), 7.44 (d, 2H). HRMS ESI+ m/z 356.2329 [MH]+.

Workup

  1. washwashed with water (15 ml)
  2. customThe layers were separated
  3. extractionthe aqueous layer was further extracted with dichloromethane (2×10 ml)
  4. washwashed with brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography on silica gel eluting with ethyl acetate:methanol:ammonia (95:5:0.5 by volume)

Sources & evidence

ORD record
ord-7c729d9210434bcfbde90092b6a1b1eb
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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