Hydrochloric Acid → (S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid

HRID 718465Notes

Reaction equation

HRID 718465 reaction equation
[OH-].[K+].[C:3]([O:7][C@@H:8]([C:15]1[C:16]([CH3:52])=[N:17][C:18]([CH3:51])=[C:19]([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH2:42][CH2:43][C:44]3[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=3)=[CH:37][CH:36]=2)[C:20]=1[N:21]1[CH2:26][CH2:25][CH:24]([C:27]2[O:31][N:30]=[C:29]([CH:32]([CH3:34])[CH3:33])[N: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]([CH3:52])=[N:17][C:18]([CH3:51])=[C:19]([C:35]2[CH:36]=[CH:37][C:38]([O:41][CH2:42][CH2:43][C:44]3[CH:45]=[CH:46][C:47]([F:50])=[CH:48][CH:49]=3)=[CH:39][CH:40]=2)[C:20]=1[N:21]1[CH2:26][CH2:25][CH:24]([C:27]2[O:31][N:30]=[C:29]([CH:32]([CH3:33])[CH3:34])[N:28]=2)[CH2:23][CH2:22]1)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 118307752(S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307745(S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acidYield 47.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

The potassium hydroxide (20.4 mg, 0.36 mmol) was added to a solution (S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate (25 mg, 0.036 mmol) in ethanol (1 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)-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid 11 mg (47%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.41-7.39 (m, 2H), 7.23-7.22 (m, 1H), 7.17-7.13 (m, 2H), 7.02-7.01 (m, 2H), 6.96-6.94/6.86-6.84/6.80-6.77 (series m, 1H), 5.73 (br. s, 1H), 4.24 (t, J=6.6 Hz, 2H), 3.67-3.65 (m, 1H), 3.07 (t, J=6.6 Hz, 2H), 3.03-2.97 (m, 1H), 2.72-2.67 (m, 2H), 2.58-2.56 (m, 1H), 2.46 (s, 3H), 2.04 (s, 3H), 1.87-1.75 (m, 4H), 1.67-1.62 (m, 1H), 1.23 (d, J=6.6 Hz, 6H), 1.12 (s, 9H). UPLC (M+H)=645.4.

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-c5563ba1cc4049f1b729125d8d59d441
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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