Hydrochloric Acid → HCID 118307879, compound

HRID 718467Notes

Reaction equation

HRID 718467 reaction equation
[OH-].[Na+].[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]([CH2:28][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[CH2:26][CH2:25][C:24]([CH2:28][CH3:29])([CH3:27])[CH2:23][CH2:22]1)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 118307712HCID 118307712, compound

Product 1

HCID 118307879HCID 118307879, compoundYield 97.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

The 1.86 mL of 1M sodium hydroxide (74 mg, 1.86 mmol) was added to a solution (S)-isopropyl 2-(tert-butoxy)-2-(4-(4-ethyl-4-methylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (128 mg, 0.207 mmol) in ethanol (2 mL) and stirred for 24 h at 90° C. An additional 0.8 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 give (S)-2-(tert-butoxy)-2-(4-(4-ethyl-4-methylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid 116 mg (97%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.38-7.35 (m, 2H), 7.20-7.18 (m, 1H), 7.13 (t, J=9.1 Hz, 2H), 7.03-7.00 (m, 3H), 5.85 (s, 1H), 4.27-4.18 (m, 2H), 3.52 (br. s, 2H), 3.27-3.21 (m, 1H), 3.04 (t, J=6.6 Hz, 2H), 2.84-2.97 (m, 1H), 2.43 (s, 3H), 2.19-2.14 (br. s, 1H), 2.05 (s, 3H), 1.96-1.91 (m, 1H), 1.49-1.38 (m, 1H), 1.29-1.23 (m, 1H), 1.17-1.12 (m, 1H), 1.12 (br. s, 9H), 1.01-0.99 (m, 1H), 0.75-0.72 (m, 3H), 0.54 (br. s, 3H). UPLC (M+H)=577.5.

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 HPLC

Sources & evidence

ORD record
ord-780e0b85557a4358b7715d1414b7a346
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

Loading…