Trifluoroacetic acid → HCID 57210991, compound

HRID 1386798Notes

Reaction equation

HRID 1386798 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:24])[CH2:9][CH2:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])(C)C)=[O:18])[CH2:13][CH2:12]2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.N1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1.[OH-].[Na+].ClC(OCC1C=CC=CC=1)=O>C(Cl)Cl.C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:24])[CH2:9][CH2:10][CH:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][CH2:20][C:23]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:18])[CH2:15][CH2:16]2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8082PiperidineHCID 10387Benzyl chloroformateHCID 14798Sodium HydroxideHCID 22458227HCID 22458227, compound

Product 1

HCID 57210991HCID 57210991, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 188 mg (0.56 mmol) of 4-(3-(4-fluorophenyl)-3-oxo-propyl)-1-(t-butoxycarbonyl) piperidine (from EXAMPLE 189, Step A) in 5 mL of CH2Cl2 at 0° C. was treated with 3 mL of TFA and the resulting mixture was stirred cold for 30 min. The solution was concentrated. A solution of the crude piperidine in 5 mL THF/5 mL of 1.0 N NaOH at 0° C. was treated with 0.09 mL (0.63 mmol) of benzyl chloroformate and the resulting mixture was stirred cold for 30 min. The reaction mixture was partitioned between 50 mL of ether and 10 mL of H2O and the layers were separated. The organic layer was washed with 10 mL of sat'd NaCl, dried and concentrated. Flash chromatography on 10 g of silica gel using 2:1 v/v hexanes/ether as the eluant afforded 196 mg (95%) of the title compound: 1H NMR (500 MHz, CDCl3) δ 1.10-1.20 (m, 21), 1.43-1.53 (m, 1H), 1.60-1.71 (4H), 2.72-2.82 (m, 2H), 2.97 (t, J=7.5, 21), 4.154.21 (m, 2H), 5.12 (s, 2H), 7.11-7.15 (m, 2H), 7.26-7.36 (5H), 7.96-8.00 (m, 2H).

Workup

  1. concentrationThe solution was concentrated
  2. stirringthe resulting mixture was stirred cold for 30 min
  3. customThe reaction mixture was partitioned between 50 mL of ether and 10 mL of H2O
  4. customthe layers were separated
  5. washThe organic layer was washed with 10 mL of sat'd NaCl
  6. customdried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-a3e9db2b4cff4202b38766b6871da238
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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