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

HRID 718460Notes

Reaction equation

HRID 718460 reaction equation
[OH-].[Na+].[C:3]([O:7][C@@H:8]([C:15]1[C:16]([CH3:46])=[N:17][C:18]([CH3:45])=[C:19]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH2:37][C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)=[CH:31][CH:30]=2)[C:20]=1[N:21]1[CH2:25][CH2:24][CH:23]([CH:26]2[CH2:28][CH2:27]2)[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]([CH3:46])=[N:17][C:18]([CH3:45])=[C:19]([C:29]2[CH:30]=[CH:31][C:32]([O:35][CH2:36][CH2:37][C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)=[CH:33][CH:34]=2)[C:20]=1[N:21]1[CH2:25][CH2:24][CH:23]([CH:26]2[CH2:28][CH2:27]2)[CH2:22]1)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 118307877(2S)-isopropyl 2-(tert-butoxy)-2-(4-(3-cyclopropylpyrrolidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307689(2S)-2-(tert-butoxy)-2-(4-(3-cyclopropylpyrrolidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acidYield 69%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

The 0.40 mL of 1M sodium hydroxide (15.93 mg, 0.40 mmol) was added to a solution of (2S)-isopropyl 2-(tert-butoxy)-2-(4-(3-cyclopropylpyrrolidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (60 mg, 0.10 mmol) in ethanol (2.5 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 afford (2S)-2-(tert-butoxy)-2-(4-(3-cyclopropylpyrrolidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid 38.3 mg (69%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.39-7.36 (m, 2H), 7.20-7.19 (m, 1H), 7.15-7.11 (m, 2H), 7.03-6.97 (m, 3H), 5.62/5.61 (s, 1H), 4.21 (t, J=6.6 Hz, 2H) 3.21-2.58 (series m, 6H), 2.44/2.43 (s, 3H), 2.06/2.04 (s, 3H), 1.69-1.64 (m, 1H), 1.41-1.22 (m, 2H), 1.10/1.09 (s, 9H), 0.51-0.45 (m, 1H), 0.32-0.23 (m, 2H), −0.50-0.15 (m, 2H). UPLC (M+H)=603.5.

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-edeea13926784426b47caa173a7667e7
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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