Sodium Hydroxide → 6-(3-Chloro-4-fluoro-phenyl)-8-methyl-8-vinyl-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid

HRID 2047701Notes

Reaction equation

HRID 2047701 reaction equation
C[O:2][C:3]([C:5]1[CH:14]=[CH:13][C:12]2[NH:11][CH:10]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[C:17]([Cl:22])[CH:16]=3)[CH2:9][C:8]([CH3:25])([CH:23]=[CH2:24])[C:7]=2[N:6]=1)=[O:4].[OH-].[Na+]>O1CCCC1.CO.O>[Cl:22][C:17]1[CH:16]=[C:15]([CH:10]2[CH2:9][C:8]([CH3:25])([CH:23]=[CH2:24])[C:7]3[N:6]=[C:5]([C:3]([OH:4])=[O:2])[CH:14]=[CH:13][C:12]=3[NH:11]2)[CH:20]=[CH:19][C:18]=1[F:21]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 665877906-(3-Chloro-4-fluoro-phenyl)-8-methyl-8-vinyl-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl ester

Product 1

HCID 565916986-(3-Chloro-4-fluoro-phenyl)-8-methyl-8-vinyl-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acidYield 64.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-(3-chloro-4-fluoro-phenyl)-8-methyl-8-vinyl-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl ester (300 mg, 0.8 mmol) in tetrahydrofuran (2 mL) and methanol (2 mL) was added 3 N sodium hydroxide (1 mL). The reaction mixture was stirred at room temperature for 16 hours, and then diluted with water (10 mL), extracted with diethyl ether (20 mL). The organic layer was discarded. The aqueous layer was acidified with concentrated hydrochloric acid to pH 4 and extracted with ethyl acetate (40 mL×3), and the combined organics were dried over anhydrous Na2SO4. The solvent was removed in vacuo and purified by preparative HPLC to afford 6-(3-chloro-4-fluoro-phenyl)-8-methyl-8-vinyl-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid (180 mg, 62.7%) as a yellow oil. MS (ESI+) [(M+H)+] 347.2.

Workup

  1. extractionextracted with diethyl ether (20 mL)
  2. extractionextracted with ethyl acetate (40 mL×3)
  3. dry with materialthe combined organics were dried over anhydrous Na2SO4
  4. customThe solvent was removed in vacuo
  5. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-16cc73e65b2d44fcb72e48e1e96fc653
Source dataset
uspto-grants-2013_11
Patent number
US08592594B2

Reaction notes

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