Lithium Hydroxide → HCID 66855759, compound

HRID 1042501Notes

Reaction equation

HRID 1042501 reaction equation
C[O:2][C:3](=[O:18])[CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=1[NH:13][CH2:14][CH2:15][CH2:16][CH3:17].[Li+].[OH-]>C1COCC1.CO>[F:12][C:9]1[CH:10]=[CH:11][C:6]([CH:5]=[CH:4][C:3]([OH:18])=[O:2])=[C:7]([NH:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH:8]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 668564993-(4-Fluoro-2-butylamino-phenyl)-acrylic acid methyl ester

Product 1

HCID 66855759HCID 66855759, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(4-fluoro-2-butylamino-phenyl)-acrylic acid methyl ester (145 mg, 0.58 mmol) in THF (4 mL) and MeOH (2 mL) was added 1 N LiOH (4 mL). The mixture was stirred for 2 hours at room temperature, concentrated under reduced pressure, and then acidified with 3 N HCl. The mixture was diluted with EtOAc, washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give 3-(4-fluoro-2-butylamino-phenyl)-acrylic acid (120 mg, 88%) after purification by crystallization form EtOAc and hexane. To a mixture of 3-(4-fluoro-2-butylamino-phenyl)-acrylic acid (52 mg, 0.22 mmol), (R)-[1-(3,5-difluoro-4-methanesulfonylaminophenyl)ethylamine hydrochloride (64 mg, 0.22 mmol) and N-methylmorpholine (36 μL, 0.33 mmol) in THF (5 mL) was added 4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methylmorpholirium chloride hydrate (DMTMM, 68 mg, 0.25 mmol). The mixture was stirred overnight at room temperature and then concentrated under reduced pressure. The residue was diluted with EtOAc and water, washed with 2 N HCl and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give the title compound (4.5 mg, 4%) after trituration with ethyl ether. 2:1).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe mixture was diluted with EtOAc
  3. washwashed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8956a7d9ced3484ab40efaa47803c175
Source dataset
uspto-grants-2013_10
Patent number
US08557872B2

Reaction notes

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