Hydrochloric Acid → 8-[(2R)-1-(3,5-difluorophenyl)pyrrolidin-2-yl]-2-morpholino-4-oxo-chromene-6-carboxylic acid

HRID 41187Notes

Reaction equation

HRID 41187 reaction equation
[OH-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([N:11]2[CH2:15][CH2:14][CH2:13][C@@H:12]2[C:16]2[CH:17]=[C:18]([C:33]([O:35]C)=[O:34])[CH:19]=[C:20]3[C:25]=2[O:24][C:23]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[CH:22][C:21]3=[O:32])[CH:7]=[C:8]([F:10])[CH:9]=1.Cl>CO.C(Cl)Cl>[F:3][C:4]1[CH:5]=[C:6]([N:11]2[CH2:15][CH2:14][CH2:13][C@@H:12]2[C:16]2[CH:17]=[C:18]([C:33]([OH:35])=[O:34])[CH:19]=[C:20]3[C:25]=2[O:24][C:23]([N:26]2[CH2:27][CH2:28][O:29][CH2:30][CH2:31]2)=[CH:22][C:21]3=[O:32])[CH:7]=[C:8]([F:10])[CH:9]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86672413methyl 8-[(2R)-1-(3,5-difluorophenyl)pyrrolidin-2-yl]-2-morpholino-4-oxo-chromene-6-carboxylate

Product 1

HCID 866724108-[(2R)-1-(3,5-difluorophenyl)pyrrolidin-2-yl]-2-morpholino-4-oxo-chromene-6-carboxylic acidYield 83.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

An aqueous NaOH 2N (2.55 ml, 5.10 mmol) solution was added to methyl 8-[(2R)-1-(3,5-difluorophenyl)pyrrolidin-2-yl]-2-morpholino-4-oxo-chromene-6-carboxylate (0.79 g, 1.68 mmol) in a mixture of MeOH (9 mL) and DCM (6 mL) and the reaction mixture was stirred at room temperature overnight. The mixture was cooled to 0° C. and an aqueous HCl 2N (2.5 mL, 5.0 mmol) solution was added dropwise to the reaction mixture until pH ˜3. After dilution with water (9 mL), the reaction mixture was concentrated to half volume. The aqueous phase was extracted with DCM, the organic phase was concentrated to dryness, leading to a foam, which was triturated in EtAc, collected by filtration, washed with EtAc, diethyl ether, dried under vacuum at 50° C. to afford 8-[(2R)-1-(3,5-difluorophenyl)pyrrolidin-2-yl]-2-morpholino-4-oxo-chromene-6-carboxylic acid (0.638 g, 83%) as an off-white solid. Mass Spectrum: m/z [M+H]+=457.

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. concentrationAfter dilution with water (9 mL), the reaction mixture was concentrated to half volume
  3. extractionThe aqueous phase was extracted with DCM
  4. concentrationthe organic phase was concentrated to dryness
  5. customwas triturated in EtAc
  6. filtrationcollected by filtration
  7. washwashed with EtAc, diethyl ether
  8. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-7b8829355c224b19ad42c396671f4b19
Source dataset
uspto-grants-2013_09
Patent number
US08530470B2

Reaction notes

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