Lithium hydroxide, monohydrate → 6-cyano-7-fluoro-3,4-dihydro-2H-chromene-4-carboxylic acid

HRID 1626386Notes

Reaction equation

HRID 1626386 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[F:13])[O:9][CH2:8][CH2:7][CH:6]2[C:14]([O:16]C)=[O:15])#[N:2].O[Li].O>C1COCC1.CCOCC.O>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[F:13])[O:9][CH2:8][CH2:7][CH:6]2[C:14]([OH:16])=[O:15])#[N:2]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 67080208Methyl 6-cyano-7-fluorochroman-4-carboxylate

Product 1

HCID 670802696-cyano-7-fluoro-3,4-dihydro-2H-chromene-4-carboxylic acidYield 81.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 6-cyano-7-fluoro-3,4-dihydro-2H-chromene-4-carboxylate (3.3 g, 14.0 mmol) and LiOH—H2O (5.89 g, 140 mmol) were stirred together in THF (25 mL) and water (25 mL) at ambient temperature for 1 hour. The reaction was diluted with ether and water, and filtered to remove undissolved solids. The filtrate was collected and the aqueous layer was washed with additional ether. The aqueous layer was acidified to pH 1-2 and the resulting solid was collected. The solid was then dissolved in ethyl acetate, dried, filtered and concentrated to provide the desired product (2.53 g, 81%) as a light yellow solid.

Workup

  1. filtrationfiltered
  2. customto remove undissolved solids
  3. customThe filtrate was collected
  4. washthe aqueous layer was washed with additional ether
  5. customthe resulting solid was collected
  6. dissolutionThe solid was then dissolved in ethyl acetate
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-b7a5e18e990144ebb6327f16e7956054
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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