Trifluoroacetic acid → 1-(6-Aminocarbonylaminoindan-1-ylmethyl)-4-(4-fluorophenyl)piperidine

HRID 351759Notes

Reaction equation

HRID 351759 reaction equation
[N-:1]=[C:2]=[O:3].[K+].FC(F)(F)C(O)=O.[NH2:12][C:13]1[CH:21]=[C:20]2[C:16]([CH2:17][CH2:18][CH:19]2[CH2:22][N:23]2[CH2:28][CH2:27][CH:26]([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[CH2:25][CH2:24]2)=[CH:15][CH:14]=1.[NH4+].[OH-]>ClCCl>[NH2:1][C:2]([NH:12][C:13]1[CH:21]=[C:20]2[C:16]([CH2:17][CH2:18][CH:19]2[CH2:22][N:23]2[CH2:28][CH2:27][CH:26]([C:29]3[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=3)[CH2:25][CH2:24]2)=[CH:15][CH:14]=1)=[O:3]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 14923Ammonium HydroxideHCID 11051572Potassio isocyanateHCID 235048071-(6-Aminoindan-1-ylmethyl)-4-(4-fluorophenyl)piperidine2×

Product 1

HCID 235048611-(6-Aminocarbonylaminoindan-1-ylmethyl)-4-(4-fluorophenyl)piperidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
5 °C

Procedure

A solution of potassium isocyanate (1.5 g) dissolved in dichloromethane (20 ml) was cooled to 5° C. and a solution of trifluoroacetic acid (1.9 g) in dichloromethane (20 ml) was added dropwise. To the resulting mixture was added dropwise a solution of 1-(6-aminoindan-1-ylmethyl)-4-(4-fluorophenyl)piperidine, 2a (3 g) in dichloromethane (10 ml). The temperature was allowed to raise to room temperature. After stirring for another 3 hours the mixture was poured on ice (500 g) and diluted aqueous NH4OH was added until pH >9. The organic phase was separated and worked-up as above. The crude title product was purified by column chromatography on silica gel (eluted with 4% triethylamine in ethanol/ethyl acetate 1:3). The purified product (2 g) was dissolved in acetone (20 ml) and added to a solution of fumaric acid (0.6 g) in ethanol (20 ml). The precipitated hemifumarate salt was filtered off and dried. Yield: 1.6 g, mp: 172-174° C. 1H NMR (DMSO-d6): δ 1.65-1.90 (m, 5H); 2.10-2.35 (m, 3H); 2.45-2.90 (m, 5H); 3.10-3.25 (m, 2H); 3.45 (qui, 1H); 6.85 (s, 2H); 6.60 (s, 1H); 7.00-7.15 (m, 4H); 7.30 (dd, 2H); 7.45 (s, 1H); 8.45 (s, 1H).

Workup

  1. temperatureto raise to room temperature
  2. additionwas added until pH >9
  3. customThe organic phase was separated
  4. customThe crude title product was purified by column chromatography on silica gel (eluted with 4% triethylamine in ethanol/ethyl acetate 1:3)
  5. dissolutionThe purified product (2 g) was dissolved in acetone (20 ml)
  6. additionadded to a solution of fumaric acid (0.6 g) in ethanol (20 ml)
  7. filtrationThe precipitated hemifumarate salt was filtered off
  8. customdried

Sources & evidence

ORD record
ord-df944a5ca9454cd1b2efa1ce07028ba6
Source dataset
uspto-grants-2004_06
Patent number
US06743808B1

Reaction notes

Loading…