Hydrochloric Acid → (S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)acetic acid

HRID 718464Notes

Reaction equation

HRID 718464 reaction equation
[OH-].[K+].[C:3]([O:7][C@@H:8]([C:15]1[C:16]([CH3:50])=[N:17][C:18]([CH3:49])=[C:19]([C:33]2[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH2:41][C:42]3[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=3)=[CH:35][CH:34]=2)[C:20]=1[N:21]1[CH2:26][CH2:25][CH:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:23][CH2:22]1)[C:9]([O:11]C(C)C)=[O:10])([CH3:6])([CH3:5])[CH3:4].Cl>C(O)C>[C:3]([O:7][C@@H:8]([C:15]1[C:16]([CH3:50])=[N:17][C:18]([CH3:49])=[C:19]([C:33]2[CH:34]=[CH:35][C:36]([O:39][CH2:40][CH2:41][C:42]3[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=3)=[CH:37][CH:38]=2)[C:20]=1[N:21]1[CH2:26][CH2:25][CH:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:23][CH2:22]1)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 118307870(S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)acetate

Product 1

HCID 118307835(S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)acetic acidYield 65%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

The potassium hydroxide (72.2 mg, 1.28 mmol) was added to a solution (S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)acetate (84 mg, 0.13 mmol) in ethanol (3 mL) and stirred for 3 h at 90° C. The reaction mixture was neutralized with 1N HCl solution, extracted with EtOAc, and the organic layer was washed with brine, and dried (MgSO4). The crude material was purified by prep HPLC to afford (S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)acetic acid 51.2 mg (65%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.41-7.39 (m, 2H), 7.28-7.22 (m, 3H), 7.17-7.13 (m, 5H), 7.05-7.01 (m, 3H), 5.88 (br. s, 1H), 4.24 (t, J=6.2 Hz, 2H), 3.59-3.58 (m, 1H), 3.09-3.06 (m, 2H), 2.75-2.71 (m, 1H), 2.58-2.56 (m, 1H), 2.47 (s, 3H), 2.26-2.22 (br. s, 1H), 2.05 (s, 3H), 1.94-1.81 (m, 2H), 1.65-1.50 (m, 3H), 1.18 (s, 9H). UPLC (M+H)=611.4.

Workup

  1. extractionextracted with EtOAc
  2. washthe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. customThe crude material was purified by prep HPLC

Sources & evidence

ORD record
ord-a4f9abe856384742befdbdd35dce3be1
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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