Lithium hydroxide, monohydrate → 3-(5-(Tert-butoxy)-5-oxopentyl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-6-carboxylic acid

HRID 927273Notes

Reaction equation

HRID 927273 reaction equation
O[Li].O.[C:4]([O:8][C:9](=[O:36])[CH2:10][CH2:11][CH2:12][CH2:13][C:14]1[N:15]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[C:16](=[O:28])[C:17]2[C:22]([CH:23]=1)=[CH:21][C:20]([C:24]([O:26]C)=[O:25])=[CH:19][CH:18]=2)([CH3:7])([CH3:6])[CH3:5]>CO.O1CCCC1.O.C(OCC)C>[C:4]([O:8][C:9](=[O:36])[CH2:10][CH2:11][CH2:12][CH2:13][C:14]1[N:15]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[C:16](=[O:28])[C:17]2[C:22]([CH:23]=1)=[CH:21][C:20]([C:24]([OH:26])=[O:25])=[CH:19][CH:18]=2)([CH3:7])([CH3:5])[CH3:6]

Participants

7

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 118558144Methyl 3-(5-(tert-butoxy)-5-oxopentyl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-6-carboxylate

Product 1

HCID 900944973-(5-(Tert-butoxy)-5-oxopentyl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-6-carboxylic acidYield 96%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

LiOH.H2O (0.229 g, 5.47 mmol) was added to a stirred, room temperature mixture of methyl 3-(5-(tert-butoxy)-5-oxopentyl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-6-carboxylate (1.24 g, 2.73 mmol) in MeOH (5 mL), tetrahydrofuran (5.00 mL) and water (5.00 mL) and the mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with diethyl ether (10 mL), water (5 mL) was added, the aqueous layer was separated, acidified with hydrochloric acid (2 M) to pH 2-3, extracted with dichloromethane (2×30 mL), the combined organic was dried (MgSO4), filtered and concentrated to give 3-(5-(tert-butoxy)-5-oxopentyl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-6-carboxylic acid (1.153 g, 2.62 mmol) as a yellow solid.

Workup

  1. additionwas added
  2. customthe aqueous layer was separated
  3. extractionextracted with dichloromethane (2×30 mL)
  4. dry with materialthe combined organic was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-27770d281e6843a1a6e159d3dc0e2154
Source dataset
uspto-grants-2016_03
Patent number
US09290454B2

Reaction notes

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