Hydrochloric Acid → (2S)-2-tert-butoxy-2-[5-[4-[2-(4-fluorophenyl)ethoxy]phenyl]-4-(4-methoxy-4-methyl-1-piperidyl)-2,6-dimethyl-3-pyridyl]acetic acid

HRID 718469Notes

Reaction equation

HRID 718469 reaction equation
[OH-].[K+].[C:3]([O:7][C@@H:8]([C:15]1[C:16]([CH3:47])=[N:17][C:18]([CH3:46])=[C:19]([C:30]2[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=3)=[CH:32][CH:31]=2)[C:20]=1[N:21]1[CH2:26][CH2:25][C:24]([O:28][CH3:29])([CH3:27])[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]([CH3:47])=[N:17][C:18]([CH3:46])=[C:19]([C:30]2[CH:31]=[CH:32][C:33]([O:36][CH2:37][CH2:38][C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=3)=[CH:34][CH:35]=2)[C:20]=1[N:21]1[CH2:22][CH2:23][C:24]([O:28][CH3:29])([CH3:27])[CH2:25][CH2:26]1)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 118307837(S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(4-methoxy-4-methylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307680(2S)-2-tert-butoxy-2-[5-[4-[2-(4-fluorophenyl)ethoxy]phenyl]-4-(4-methoxy-4-methyl-1-piperidyl)-2,6-dimethyl-3-pyridyl]acetic acidYield 21.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

The potassium hydroxide (230 mg, 4.1 mmol) was added to a gave (S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(4-methoxy-4-methylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate (255 mg, 0.41 mmol) in ethanol (4 mL) and stirred for 6 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 to give (S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(4-methoxy-4-methylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid 51 mg (21%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.39-7.36 (m, 2H), 7.19-7.12 (m, 3H), 7.02-6.99 (m, 3H), 5.81 (s, 1H), 4.24-4.21 (m, 2H), 3.49 (br. s, 4H), 3.07-3.04 (m, 2H), 2.89/2.81 (s, 3H), 2.44 (s, 3H), 2.04 (s, 3H), 1.59-1.45 (m, 3H), 1.32-1.25 (m, 1H), 1.12 (br. s, 9H), 0.99/0.81 (s, 3H). UPLC (M+H)=579.5.

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

Sources & evidence

ORD record
ord-80cdfc961b8f4c8e8e8ea1515b2e8d96
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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