Hydrochloric Acid → 4-[4-[4-(Hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha, alpha-dimethylbenzeneacetic Acid, Methyl Ester Hydrochloride

HRID 411920Notes

Reaction equation

HRID 411920 reaction equation
[ClH:1].[OH:2][C:3]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=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]([CH3:27])([CH3:26])[C:22]([O:24][CH3:25])=[O:23])=[CH:17][CH:16]=2)=[O:14])[CH2:6][CH2:5]1.[BH4-].[Na+].[OH-].[Na+].Cl>CO>[ClH:1].[OH:2][C:3]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=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]([CH3:27])([CH3:26])[C:22]([O:24][CH3:25])=[O:23])=[CH:17][CH:16]=2)[OH:14])[CH2:6][CH2:5]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 22471930Methyl 2-(4-(4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butanoyl)phenyl)-2-methylpropanoate hydrochloride

Product 1

HCID 865835134-[4-[4-(Hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha, alpha-dimethylbenzeneacetic Acid, Methyl Ester HydrochlorideYield 94%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-10 °C

Procedure

Dissolve 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethylbenzeneacetic acid, methyl ester hydrochloride (550 mg, 1.00 mmol) in methanol (5 mL) and add sodium borohydride (62.8 mg) in three batches. Stir for 1 hour, add 50% aqueous sodium hydroxide (800 mg) and heat to reflux with stirring. After 3 hours, cool to −10° C., add approximately 1.5 mL of 6 N HCl over 10 minutes, filter the solid and wash with ice water (12 mL) such that the final filtrate is pH=5. Dry the resulting solid in vacuo (50-60° C., 10−1 mm) overnight to give the title compound (515 mg, 94%); mp 165-180° C. 1H NMR (300 MHz, 5% MeOD4 in CDCl3) δ 7.50 (d, J=7.3 Hz, 4H), 7.30 (m, 8H), 7.18 (t, J=7.0 Hz, 2H), 4.66 (t, J=5.3 Hz, 1H), 3.47 (m, 6H), 2.97 (m, 2H), 2.69 (m, 3H), 1.6-2.2 (m, 6H), 1.55 (s, 6H); 13C NMR (75 MHz, 5% MeOD4 in CDCl3) δ 179.1, 145.3, 143.8, 142.3, 128.2, 126.6, 125.7, 125.5, 125.5, 125.4, 78.4 (bis benzylic), 72.5 (benzylic), 57.4, 53.2, 46.2, 24.2, 35.9, 26.6, 24.1, 20.8: MS (CI/NH3) 502 (100− (M+H)), 280 (5), 200 (10).

Workup

  1. temperatureheat
  2. temperatureto reflux
  3. stirringwith stirring
  4. waitAfter 3 hours
  5. filtrationfilter the solid
  6. washwash with ice water (12 mL) such that the final filtrate
  7. customDry the resulting solid in vacuo (50-60° C., 10−1 mm) overnight

Sources & evidence

ORD record
ord-d7b560a350b94867b2fdcd3ab0de8820
Source dataset
uspto-grants-2003_05
Patent number
US06559312B2

Reaction notes

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