Hydrochloric Acid → 8-(1-(3,5-difluorophenylamino)ethyl)-2-((S)-3-methylmorpholino)-4-oxo-4H-chromene-6-carboxylic acid

HRID 1947376Notes

Reaction equation

HRID 1947376 reaction equation
[OH-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([NH:11][CH:12]([C:14]2[CH:15]=[C:16]([C:32]([O:34]C)=[O:33])[CH:17]=[C:18]3[C:23]=2[O:22][C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][C@@H:25]2[CH3:30])=[CH:20][C:19]3=[O:31])[CH3:13])[CH:7]=[C:8]([F:10])[CH:9]=1.C1COCC1.Cl>CO>[F:3][C:4]1[CH:5]=[C:6]([NH:11][CH:12]([C:14]2[CH:15]=[C:16]([C:32]([OH:34])=[O:33])[CH:17]=[C:18]3[C:23]=2[O:22][C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][C@@H:25]2[CH3:30])=[CH:20][C:19]3=[O:31])[CH3:13])[CH:7]=[C:8]([F:10])[CH:9]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 58235042methyl 8-(1-(3,5-difluorophenylamino)ethyl)-2-((S)-3-methylmorpholino)-4-oxo-4H-chromene-6-carboxylate

Product 1

HCID 582350018-(1-(3,5-difluorophenylamino)ethyl)-2-((S)-3-methylmorpholino)-4-oxo-4H-chromene-6-carboxylic acidYield 86%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2N NaOH (0.206 mL, 0.41 mmol) was added to a stirred suspension of methyl 8-(1-(3,5-difluorophenylamino)ethyl)-2-((S)-3-methylmorpholino)-4-oxo-4H-chromene-6-carboxylate (90 mg, 0.20 mmol) in MeOH (1 mL)/THF (1 mL) and cooled with an ice-water bath. The resulting suspension was stirred at RT for 2 hours. The reaction was incomplete thus the temperature was increased to 35° C. and stirred for an additional hour. The reaction mixture was cooled with an ice bath, the pH was adjusted to 2-3 with hydrochloric acid 1M and the volatils were evaporated. The resulting precipitate was collected by filtration, dried, triturated with diethyl ether, collected by filtration and dried again under vacuum to give 8-(1-(3,5-difluorophenylamino)ethyl)-2-((S)-3-methylmorpholino)-4-oxo-4H-chromene-6-carboxylic acid (75 mg, 86%). Mass Spectrum: M+H+ 445.

Workup

  1. temperaturecooled with an ice-water bath
  2. temperaturewas increased to 35° C.
  3. stirringstirred for an additional hour
  4. temperatureThe reaction mixture was cooled with an ice bath
  5. customthe volatils were evaporated
  6. filtrationThe resulting precipitate was collected by filtration
  7. customdried
  8. customtriturated with diethyl ether
  9. filtrationcollected by filtration
  10. customdried again under vacuum

Sources & evidence

ORD record
ord-9e57bd26e1464075a054d6e14486bc07
Source dataset
uspto-grants-2013_03
Patent number
US08399460B2

Reaction notes

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