Sodium Hydroxide → HCID 10226037, compound

HRID 478914Notes

Reaction equation

HRID 478914 reaction equation
C([O:3][C:4]([C:6]1([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[CH2:11][CH2:10][N:9]([CH2:12][CH:13]2[O:17][N:16]=[C:15]([C:18]3[CH:27]=[CH:26][C:21]4[NH:22][C:23](=[O:25])[O:24][C:20]=4[CH:19]=3)[CH2:14]2)[CH2:8][CH2:7]1)=[O:5])C.[OH-].[Na+]>CCO>[F:35][C:32]1[CH:33]=[CH:34][C:29]([CH2:28][C:6]2([C:4]([OH:5])=[O:3])[CH2:7][CH2:8][N:9]([CH2:12][CH:13]3[O:17][N:16]=[C:15]([C:18]4[CH:27]=[CH:26][C:21]5[NH:22][C:23](=[O:25])[O:24][C:20]=5[CH:19]=4)[CH2:14]3)[CH2:10][CH2:11]2)=[CH:30][CH:31]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 10299528HCID 10299528, compound

Product 1

HCID 10226037HCID 10226037, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 4-(4-fluorobenzyl)-1-[3-(2-oxo-2,3-dihydrobenzoxazol-6-yl)-4,5-dihydroisoxazol-5-ylmethyl]piperidine-4-carboxylic acid ethyl ester (390 mg, 0.81 mmol) and 20% aq. NaOH (4.5 mL) in EtOH (4.5 mL) was heated to reflux for 16 hours. After stirring at ambient temperature overnight, the reaction solvent was removed under reduced pressure. The reaction mixture was diluted with water, brought to pH 3 with 1N HCl, and extracted with EtOAc (2×). The combined extracts were dried (Na2SO4) and concentrated under reduced pressure. Purification by chromatography (silica, 79:20:1 CH2Cl2/MeOH/AcOH) followed by recrystallization from MeOH/Et2O gave 4-(4-fluorobenzyl)-1-[3-(2-oxo-2,3-dihydrobenzoxazol-6-yl)-4,5-dihydroisoxazol-5-ylmethyl]piperidine-4-carboxylic acid (28 mg, 8%) as a yellow solid:

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 16 hours
  3. customthe reaction solvent was removed under reduced pressure
  4. additionThe reaction mixture was diluted with water
  5. extractionextracted with EtOAc (2×)
  6. dry with materialThe combined extracts were dried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customPurification by chromatography (silica, 79:20:1 CH2Cl2/MeOH/AcOH)
  9. customfollowed by recrystallization from MeOH/Et2O

Sources & evidence

ORD record
ord-9d702f0a4b6843289860a0685b6d4a87
Source dataset
uspto-grants-2003_11
Patent number
US06642256B2

Reaction notes

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