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

HRID 718472Notes

Reaction equation

HRID 718472 reaction equation
[OH-].[K+].[CH2:3]([CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[C:21]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)=[CH:24][CH:23]=3)=[C:20]([CH3:38])[N:19]=[C:18]([CH3:39])[C:17]=2[C@H:40]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[C:41]([O:43]C(C)C)=[O:42])[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl>C(O)C>[CH2:3]([CH:10]1[CH2:11][CH2:12][N:13]([C:16]2[C:21]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)=[CH:24][CH:23]=3)=[C:20]([CH3:38])[N:19]=[C:18]([CH3:39])[C:17]=2[C@H:40]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[C:41]([OH:43])=[O:42])[CH2:14][CH2:15]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 118307842(S)-isopropyl 2-(4-(4-benzylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118307696(S)-2-(4-(4-benzylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetic acidYield 25.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

The potassium hydroxide (86 mg, 1.54 mmol) was added to a station (S)-isopropyl 2-(4-(4-benzylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (102 mg, 0.154 mmol) in ethanol (3 mL) and stirred for 12 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 give (S)-2-(4-(4-benzylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetic acid 24.3 mg (25%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.40-7.37 (m, 2H), 7.24-7.22 (m, 2H), 7.18-7.12 (m, 4H), 7.10 (t, J=7.7 Hz, 2H), 6.99-6.92 (m, 3H), 5.77 (s, 1H), 4.21 (t, J=6.6 Hz, 2H), 3.47-3.37 (m, 4H), 3.06 (t, J=6.2 Hz, 2H), 2.46-2.44 (m, 2H), 2.42 (s, 3H), 2.01 (s, 3H), 1.66 (t, J=10.6 Hz, 1H), 1.44-1.41 (m, 1H), 1.34-1.22 (m, 3H), 1.09 (m, 9H). UPLC (M+H)=625.4.

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-c40fcb6c5fcd47b3a09c795f0623429f
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

Loading…