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

HRID 718462Notes

Reaction equation

HRID 718462 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]([CH3:26])([CH3:25])[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: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]([CH3:26])([CH3:25])[CH2:22]1)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 118307700(S)-isopropyl 2-(tert-butoxy)-2-(4-(3,3-dimethylazetidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307872(2S)-2-tert-butoxy-2-[4-(3,3-dimethylazetidin-1-yl)-5-[4-[2-(4-fluorophenyl)ethoxy]phenyl]-2,6-dimethyl-3-pyridyl]acetic acidYield 74.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

The 0.60 mL of 1M sodium hydroxide (16.64 mg, 0.42 mmol) was added to a solution (S)-isopropyl 2-(tert-butoxy)-2-(4-(3,3-dimethylazetidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (60 mg, 0.10 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 HPLC to give (S)-2-(tert-butoxy)-2-(4-(3,3-dimethylazetidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid 40 mg (72%). 1H NMR (500 MHz, DMSO-d6) δ 7.40-7.37 (m, 2H), 7.26 (br. s, 1H), 7.14 (t, J=8.8 Hz, 2H), 7.0 (d, J=9.2 Hz, 1H), 6.96 (d, J=6.6 Hz, 1H), 6.86 (br. s, 1H), 5.04 (s, 1H), 4.21 (t, J=6.2 Hz, 2H) 3.47 (br. s, 4H), 3.05 (t, J=6.2 Hz, 2H), 2.01 (s, 3H), 1.91 (s, 3H), 1.10 (s, 9H), 1.02 (s, 6H). UPLC (M+H)=535.45.

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-9e1902f4ade744b0ada16a90808e90d5
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

Loading…