Lithium hydroxide, monohydrate → 7-((3-(tert-Butoxycarbonyl)azetidin-1-yl)methyl)-4,5-dihydronaphtho[2,1-d]isoxazole-3-carboxylic acid

HRID 1506393Notes

Reaction equation

HRID 1506393 reaction equation
[C:1]([O:5][C:6]([CH:8]1[CH2:11][N:10]([CH2:12][C:13]2[CH:14]=[C:15]3[C:23](=[CH:24][CH:25]=2)[C:22]2[O:21][N:20]=[C:19]([C:26]([O:28]C)=[O:27])[C:18]=2[CH2:17][CH2:16]3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+]>C1COCC1.O>[C:1]([O:5][C:6]([CH:8]1[CH2:11][N:10]([CH2:12][C:13]2[CH:14]=[C:15]3[C:23](=[CH:24][CH:25]=2)[C:22]2[O:21][N:20]=[C:19]([C:26]([OH:28])=[O:27])[C:18]=2[CH2:17][CH2:16]3)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 67168670Methyl 7-((3-(tert-butoxycarbonyl)azetidin-1-yl)methyl)-4,5-dihydronaphtho[2,1-d]isoxazole-3-carboxylate

Product 1

HCID 681821157-((3-(tert-Butoxycarbonyl)azetidin-1-yl)methyl)-4,5-dihydronaphtho[2,1-d]isoxazole-3-carboxylic acidYield 120.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of methyl 7-((3-(tert-butoxycarbonyl)azetidin-1-yl)methyl)-4,5-dihydronaphtho[2,1-d]isoxazole-3-carboxylate (Preparation 45D, 95 mg, 0.238 mmol) and lithium hydroxide monohydrate (12.01 mg, 0.286 mmol) in THF (3 mL) and water (1.500 mL) was allowed to stir at room temperature overnight. The THF was evaporated and the residue diluted with 5 ml of water. The pH was adjusted to 5-6 and extracted with ethyl acetate six times. The organic layers were combined, dried over sodium sulfate and concentrated to afford 110 mg of product (HPLC purity 75-80%). The compound had an HPLC ret. time=0.67/2.0 min. (condition E); MS:(M+H)=385.3.

Workup

  1. customThe THF was evaporated
  2. additionthe residue diluted with 5 ml of water
  3. extractionextracted with ethyl acetate six times
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-6fa7084d882d47619677b02b64f6a6c4
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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