Hydrochloric Acid → 3-(4-{4-[4-(2-Hydroxy-3,3-dimethylbutoxy)-3-methylphenyl]-piperidin-4-YL}-2-methylphenoxy)-propane-1,2(S)-diol

HRID 250185Notes

Reaction equation

HRID 250185 reaction equation
[OH-].[Na+].[OH:3][C@@H:4]([CH2:38][OH:39])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH:30]([OH:35])[C:31]([CH3:34])([CH3:33])[CH3:32])=[C:24]([CH3:36])[CH:23]=3)[CH2:18][CH2:17][N:16](C(=O)C)[CH2:15][CH2:14]2)=[CH:9][C:8]=1[CH3:37].Cl>CO>[OH:35][CH:30]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:29][O:28][C:25]1[CH:26]=[CH:27][C:22]([C:13]2([C:10]3[CH:11]=[CH:12][C:7]([O:6][CH2:5][C@@H:4]([OH:3])[CH2:38][OH:39])=[C:8]([CH3:37])[CH:9]=3)[CH2:14][CH2:15][NH:16][CH2:17][CH2:18]2)=[CH:23][C:24]=1[CH3:36]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 668894711-(4-{4-[2(S),3-dihydroxy-propoxy]-3-methylphenyl}-4-[4-(2-hydroxy-3,3-dimethylbutoxy)-3-methylphenyl]piperidin-1-yl)ethanone

Product 1

HCID 668889253-(4-{4-[4-(2-Hydroxy-3,3-dimethylbutoxy)-3-methylphenyl]-piperidin-4-YL}-2-methylphenoxy)-propane-1,2(S)-diolYield 30%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1N NaOH (8 mL) in MeOH (2 mL) was added 1-(4-{4-[2(S),3-dihydroxy-propoxy]-3-methylphenyl}-4-[4-(2-hydroxy-3,3-dimethylbutoxy)-3-methylphenyl]piperidin-1-yl)ethanone (30 mg, 0.058 mmol). The reaction mixture was heated at 80° C. for 16 h, cooled, acidified with 1N HCl (8-9 mL), and washed with EtOAc. The aqueous layer was lyophilized and the crude material was purified by reverse-phase HPLC (C18 column), eluting with 0.05% TFA in MeCN—H2O (1:9 to 9:1) to provide the title compound (8.2 mg, 24%) as its TFA salt: 1H-NMR (DMSO-d6) δ 8.31 (2H, br s), 7.00 (4H, m), 6.78 (2H, app t), 4.70-4.90 (2H, m), 4.56-4.66 (1H, m), 3.88-4.04 (2H, m), 3.70-3.86 (3H, m), 3.00 (4H, br s), 2.47 (4H, br s), 2.12 (3H, s), 2.11 (3H, s), 2.09 (1H, br s), 0.91 (9H, s); MS(ESI): 472 (MH+).

Workup

  1. temperaturecooled
  2. washwashed with EtOAc
  3. customthe crude material was purified by reverse-phase HPLC (C18 column)
  4. washeluting with 0.05% TFA in MeCN—H2O (1:9 to 9:1)

Sources & evidence

ORD record
ord-557d5d83af4a49c09689c864303b5ece
Source dataset
uspto-grants-2011_01
Patent number
US07863298B2

Reaction notes

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