Sodium Hydroxide → Mk-8245

HRID 561212Notes

Reaction equation

HRID 561212 reaction equation
[Br:1][C:2]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:15]=[C:14]([C:16]3[N:17]=[N:18][N:19]([CH2:21][C:22]([O:24]CC)=[O:23])[N:20]=3)[O:13][N:12]=2)[CH2:7][CH2:6]1.[OH-].[Na+]>C1COCC1.CO>[Br:1][C:2]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:15]=[C:14]([C:16]3[N:17]=[N:18][N:19]([CH2:21][C:22]([OH:24])=[O:23])[N:20]=3)[O:13][N:12]=2)[CH2:7][CH2:6]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 53388532Ethyl (5-{3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]isoxazol-5-yl}-2H-tetrazol-2-yl)acetate

Product 1

HCID 24988881Mk-8245

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl (5-{3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]isoxazol-5-yl}-2H-tetrazol-2-yl)acetate (1.3 g, 2.62 mmol) in THF (15 mL) and MeOH (5 mL) was added 1M sodium hydroxide (5.25 mL, 5.25 mmol). The mixture was stirred at room temperature for 1 h. Volatile solvents were removed in vacuo. The residue was diluted with water (20 mL), acidified with 1M HCl (6 mL) and extracted with EtOAc. The EtOAc extract was washed with water, dried (Na2SO4) and concentrated. The residue was triturated with diethyl ether to give the crude product, containing about 5% of the 1-isomer. Further purification by trituration in isopropyl acetate (2×, 80° C. overnight, then room temperature overnight) provided the title compound as a beige powder.

Workup

  1. customVolatile solvents were removed in vacuo
  2. additionThe residue was diluted with water (20 mL)
  3. extractionextracted with EtOAc
  4. extractionThe EtOAc extract
  5. washwas washed with water
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe residue was triturated with diethyl ether
  9. customto give the crude product
  10. customFurther purification by trituration in isopropyl acetate (2×, 80° C. overnight

Sources & evidence

ORD record
ord-c0732cf615164cf896a991687af1f34e
Source dataset
uspto-grants-2011_11
Patent number
US08063224B2

Reaction notes

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