Water → 1-(6-Acetylaminoindan-1-ylmethyl)-4-(4-fluorophenyl)piperidine

HRID 324359Notes

Reaction equation

HRID 324359 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH:8]2[CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:32](Cl)(=[O:34])[CH3:33].O>ClCCl>[C:32]([NH:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH:8]2[CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)[CH2:14][CH2:13]2)=[CH:4][CH:3]=1)(=[O:34])[CH3:33]

Participants

6

Reactant 4

HCID 962WaterHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 235048071-(6-Aminoindan-1-ylmethyl)-4-(4-fluorophenyl)piperidine2×

Product 1

HCID 232165841-(6-Acetylaminoindan-1-ylmethyl)-4-(4-fluorophenyl)piperidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-(6-aminoindan-1-ylmethyl)-4-(4-fluorophenyl)piperidine, 2a (6.5 g) and triethylamine (3 ml) in dichloromethane (150 ml) cooled to 0° C. was added dropwise a solution of acetylchloride (1.7 g) in dichloromethane (50 ml). The mixture was stirred for one hour at room temperature. Water (500 ml) was added, the organic phase separated, washed with brine (2×50 ml) and finally worked-up as above. The thus isolated crude title product was purified by column chromatography on silica gel (eluted with a mixture of ethyl acetate/heptane/ triethylamine 75:25:4). Recrystallization from diethyl ether yielded 7.7 g of pure title compound 4a. Mp: 159-162° C. 1H NMR (CDCl3): δ 1.70-1.90 (m, 5 H); 2.00-2.15 (m, 1 H); 2.15 (s, 3 H); 2.20-2.30 (m, 1 H); 2.35-2.50 (m, 2 H); 2.60 (dd, 1 H); 2.70-2.90 (m, 2 H); 2.95-3.15 (m, 2 H); 3.45 (qui, 1 H); 6.95 (t, 2 H); 7.05-7.25 (m,5 H); 7.55 (s, 1 H)

Workup

  1. customthe organic phase separated
  2. washwashed with brine (2×50 ml)
  3. customThe thus isolated crude title product
  4. customwas purified by column chromatography on silica gel (
  5. washeluted with a mixture of ethyl acetate/heptane/ triethylamine 75:25:4)
  6. customRecrystallization from diethyl ether

Sources & evidence

ORD record
ord-6d457f53f9404fffb88639949a684759
Source dataset
uspto-grants-2001_04
Patent number
US06218394B1

Reaction notes

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