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

HRID 718468Notes

Reaction equation

HRID 718468 reaction equation
[OH-].[Na+].[C:3]([O:7][C@@H:8]([C:15]1[C:16]([CH3:45])=[N:17][C:18]([CH3:44])=[C:19]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)=[CH:30][CH:29]=2)[C:20]=1[N:21]1[CH2:26][CH2:25][CH:24]([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]([CH3:45])=[N:17][C:18]([CH3:44])=[C:19]([C:28]2[CH:29]=[CH:30][C:31]([O:34][CH2:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)=[CH:32][CH:33]=2)[C:20]=1[N:21]1[CH2:26][CH2:25][CH:24]([CH3:27])[CH2:23][CH2:22]1)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 118307686(S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetate

Product 1

HCID 118307846(S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetic acidYield 48%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

The 1.32 mL of 1M sodium hydroxide (52.8 mg, 1.32 mmol) was added to a (S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetate (130 mg, 0.22 mmol) in ethanol (1 mL) and stirred for 24 h at 85° C. An additional 0.31 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 HPLC to afford (S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetic acid 58 mg (48%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.40-7.37 (m, 2H), 7.19 (d, J=9.2 Hz, 1H), 7.14 (t, J=8.8 Hz, 2H), 7.00-6.95 (m, 3H), 5.84 (s, 1H), 4.22 (t, J=6.6 Hz, 2H), 3.44-3.39 (m, 4H), 3.06 (t, J=6.6 Hz, 2H), 2.43 (s, 3H), 2.03 (s, 3H), 1.72-1.68 (m, 1H), 1.49 (d, J=12.1 Hz, 1H), 1.34 (d, J=7.0 Hz, 1H), 1.24-1.20 (m, 1H), 1.12 (s, 9H), 1.06-1.01 (m, 1H), 0.83 (d, J=3.7 Hz, 3H). UPLC (M+H)=549.6.

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 HPLC

Sources & evidence

ORD record
ord-4a7fde5b43124059bc4b700d7353924f
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

Loading…