Hydrochloric Acid → 4-[(4-(Hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha,alpha-dimethylbenzeneacetic acid hydrochloride hydrate

HRID 722696Notes

Reaction equation

HRID 722696 reaction equation
[ClH:1].[OH:2][C:3]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][C:13]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([CH3:28])([CH3:27])[C:22]([O:24]CC)=[O:23])=[CH:17][CH:16]=2)=[O:14])[CH2:6][CH2:5]1.[OH-].[Na+].[BH4-].[Na+].Cl>O.CC(C)=O.CO>[OH2:2].[ClH:1].[OH:2][C:3]([C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][CH:13]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([CH3:28])([CH3:27])[C:22]([OH:24])=[O:23])=[CH:17][CH:16]=2)[OH:14])[CH2:6][CH2:5]1

Participants

8

Reactant 4

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 12939646Ethyl 4-{4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl}-alpha,alpha-dimethylbenzeneacetate hydrochloride

Product 1

HCID 116137484-[(4-(Hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha,alpha-dimethylbenzeneacetic acid hydrochloride hydrateYield 193.2%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 887MethanolSolventHCID 962WaterSolvent4×

Conditions

Temperature
35 °C

Procedure

Mix ethyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethylbenzeneacetate, hydrochloride (101.92 g, 0.1807 mol) and methanol (510 mL) and stir. Rapidly add 50% sodium hydroxide (72.27 g, 0.903 mol) and wash in with water (61 mL). Heat to reflux for 2 hours, allow to cool to 35° C. and treat with sodium borohydride (3.42 g, 0.0903 mol). Add water (100 mL) and maintain at 35° C. for 10 hours. Add 37% hydrochloric acid (53.0 g) to adjust pH to 11.5. Add acetone (26.5 mL) and water (102 mL). Hold at 35° C. for 2 hours and adjust to pH 2.5 with 37% hydrochloric acid (44.69 g). Dilute with water (408 mL), cool to −15° C., stir for 1.5 hours and collect the precipitate by vacuum filtration. Wash the filtercake with deionized water (3×100 mL) and vacuum dry to give 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride hydrate (97.10 g).

Workup

  1. temperatureHeat
  2. temperatureto reflux for 2 hours
  3. temperaturecool to −15° C.
  4. stirringstir for 1.5 hours
  5. customcollect the precipitate
  6. filtrationby vacuum filtration
  7. washWash the filtercake with deionized water (3×100 mL) and vacuum
  8. customdry

Sources & evidence

ORD record
ord-c64febde4c25436cb1e055ff9e150b8c
Source dataset
uspto-grants-2006_11
Patent number
US07138524B2

Reaction notes

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