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

HRID 718466Notes

Reaction equation

HRID 718466 reaction equation
[OH-].[Na+].[C:3]([O:7][C@@H:8]([C:15]1[C:16]([CH3:48])=[N:17][C:18]([CH3:47])=[C:19]([C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][C:40]3[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=3)=[CH:33][CH:32]=2)[C:20]=1[N:21]1[CH2:26][CH2:25][CH:24]([C:27]([F:30])([F:29])[F:28])[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]([CH3:48])=[N:17][C:18]([CH3:47])=[C:19]([C:31]2[CH:32]=[CH:33][C:34]([O:37][CH2:38][CH2:39][C:40]3[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=3)=[CH:35][CH:36]=2)[C:20]=1[N:21]1[CH2:22][CH2:23][CH:24]([C:27]([F:30])([F:29])[F:28])[CH2:25][CH2:26]1)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 118307717(S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)-phenyl)-2,6-dimethyl-4-(4-(trifluoromethyl)piperidin-1-yl)pyridin-3-yl)acetate

Product 1

HCID 118307704(S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-(trifluoromethyl)piperidin-1-yl)pyridin-3-yl)acetic acidYield 89.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

The 0.23 mL of 1M sodium hydroxide (9.3 mg, 0.23 mmol) was added to a solution (S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-(trifluoromethyl)piperidin-1-yl)pyridin-3-yl)acetate (50 mg, 0.078 mmol) in ethanol (1 mL) and stirred for 24 h at 90° C. An additional 0.23 mL sodium hydroxide was added and the reaction was continued for 24 h. 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 afford (S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-(trifluoromethyl)piperidin-1-yl)pyridin-3-yl)acetic acid 42 mg (89%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.41-7.38 (m, 2H), 7.21-7.20 (m, 1H), 7.14 (t, J=8.8 Hz, 2H), 7.0 (d, J=8.4 Hz, 2H), 6.95 (d, J=7.7 Hz, 1H), 5.54 (br. s, 1H), 4.23 (t, J=6.7 Hz, 2H), 3.96-3.94 (m, 2H), 3.07 (t, J=6.6 Hz, 2H), 2.90/2.74 (s, 2H), 2.46 (s, 3H), 2.55 (br. s, 1H), 2.03 (s, 3H), 1.72-1.61 (m, 3H), 1.56-1.54 (m, 1H), 1.10 (s, 9H). UPLC (M+H)=603.5.

Workup

  1. waitthe reaction was continued for 24 h
  2. extractionextracted with EtOAc
  3. washthe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. customThe crude material was purified by prep

Sources & evidence

ORD record
ord-b8d0d18841ba4823aafdf991bc1dd0e6
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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