Hydrochloric Acid → (2S)-2-tert-butoxy-2-[4-(3,3-difluoroazetidin-1-yl)-5-[4-[2-(4-fluorophenyl)ethoxy]phenyl]-2,6-dimethyl-3-pyridyl]acetic acid

HRID 718461Notes

Reaction equation

HRID 718461 reaction equation
[OH-].[Na+].[C:3]([O:7][C@@H:8]([C:15]1[C:16]([CH3:44])=[N:17][C:18]([CH3:43])=[C:19]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH2:35][C:36]3[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=3)=[CH:29][CH:28]=2)[C:20]=1[N:21]1[CH2:24][C:23]([F:26])([F:25])[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]([CH3:44])=[N:17][C:18]([CH3:43])=[C:19]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH2:35][C:36]3[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=3)=[CH:29][CH:28]=2)[C:20]=1[N:21]1[CH2:22][C:23]([F:26])([F:25])[CH2:24]1)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 118307864(S)-isopropyl 2-(tert-butoxy)-2-(4-(3,3-difluoroazetidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307678(2S)-2-tert-butoxy-2-[4-(3,3-difluoroazetidin-1-yl)-5-[4-[2-(4-fluorophenyl)ethoxy]phenyl]-2,6-dimethyl-3-pyridyl]acetic acidYield 94.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

The 0.40 mL of 1M sodium hydroxide (14.78 mg, 0.37 mmol) was added to a solution (S)-isopropyl 2-(tert-butoxy)-2-(4-(3,3-difluoroazetidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (54 mg, 0.09 mmol) in ethanol (2 mL) and stirred for 18 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 to afford (S)-2-(tert-butoxy)-2-(4-(3,3-difluoroazetidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid 46 mg (92%). 1H NMR (500 MHz, DMSO-d6) δ 7.40-7.37 (m, 2H), 7.28 (d, J=8.4 Hz, 1H), 7.14 (t, J=8.8 Hz, 2H), 7.04-6.95 (m, 3H), 5.03 (s, 1H), 4.23 (t, J=6.6 Hz, 2H) 4.04 (t, J=12.8 Hz, 4H), 3.06 (t, J=6.6 Hz, 2H), 2.40 (s, 3H), 2.05 (s, 3H), 1.09 (s, 9H). UPLC (M+H)=544.05.

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

Sources & evidence

ORD record
ord-f4fc57ef3f14460e89d7c7ce237c9ec5
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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