Hydrochloric Acid → 4-(2,3-Dimethoxybenzoyl)piperidine

HRID 51281Notes

Reaction equation

HRID 51281 reaction equation
[CH3:1][O:2][C:3]1[C:23]([O:24][CH3:25])=[CH:22][CH:21]=[CH:20][C:4]=1[C:5]([CH:7]1[CH2:12][CH2:11][N:10](C(OC(C)(C)C)=O)[CH2:9][CH2:8]1)=[O:6].Cl.[OH-].[Na+]>C1(C)C=CC=CC=1.O>[CH3:1][O:2][C:3]1[C:23]([O:24][CH3:25])=[CH:22][CH:21]=[CH:20][C:4]=1[C:5]([CH:7]1[CH2:8][CH2:9][NH:10][CH2:11][CH2:12]1)=[O:6]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 46780868N-Boc-(2,3-dimethoxyphenyl)-4-piperidinylmethanone

Product 1

HCID 227378494-(2,3-Dimethoxybenzoyl)piperidineYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 1140TolueneSolvent2×

Conditions

Temperature
60 °C

Procedure

To the reaction solution of 4-(2,3-dimethoxybenzoyl)-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester (7) from Example 76, Scheme G, step c, is added about 188 kg of water and 37% hydrochloric acid (39 kg, 395 mol). The solution is heated to about 60° C. for about 18 hours1. The mixture is cooled to about 25° C. and about 47 kg of toluene is added. The phases are separated and the organic phase is discarded. To the aqueous phase is added about 78 kg water, 50 wt % sodium hydroxide solution (31 kg, 391 mol), and about 99 kg of toluene. The phases are separated and the aqueous phase is discarded. The organic phase is concentrated by vacuum distillation. The concentration of 4-(2,3-dimethoxybenzoyl)piperidine (16) in solution ranges from 17 to 53 wt %1, affording 14.6 to 17.9 kg of 4-(2,3-dimethoxybenzoyl)piperidine (16) (65-76% yield).

Workup

  1. temperatureThe mixture is cooled to about 25° C.
  2. customThe phases are separated
  3. customThe phases are separated
  4. concentrationThe organic phase is concentrated by vacuum distillation

Sources & evidence

ORD record
ord-291413b63c804674aaedaf5da5d78dee
Source dataset
uspto-grants-2004_03
Patent number
US06713627B2

Reaction notes

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