Potassium Hydroxide → Ammonia

HRID 265014Notes

Reaction equation

HRID 265014 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:21]([O:23]C)=O)=[C:6]2[C:11]=1[O:10][CH2:9][C@H:8]([N:12]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[CH2:13][CH2:14][CH3:15])[CH2:7]2.[OH-].[K+].O=S(Cl)Cl.FC1C=CC(C(O)=O)=C2C=1OC[C@H]([N:42](C(CC)CC)CCC)C2>CO.O.C(Cl)Cl.CN(C=O)C>[NH3:12].[C:21]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[C:11]2[C:6]=1[CH2:7][C@@H:8]([N:12]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[CH2:13][CH2:14][CH3:15])[CH2:9][O:10]2)(=[O:23])[NH2:42]

Participants

10

Reactant 4

HCID 14797Potassium HydroxideHCID 24386Thionyl ChlorideHCID 53656554(R)-8-fluoro-5-carboxy-3-(N-3-pentyl-N-n-propylamino)chromanHCID 53912065(R)-8-Fluoro-5-methoxycarbonyl-3-(N-3-pentyl-N-n-propylamino)chroman

Product 2

HCID 222AmmoniaHCID 22853658(R)-5-Carbamoyl-8-Fluoro-3-(N-3-pentyl-N-n-propylamino)chroman

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

(R)-8-Fluoro-5-methyloxycarbonyl-3-(N-3-pentyl-N-n-propylamino)chroman (0.72 g, 2.13 mmol) was hydrolysed with KOH (0.20 g, 3.1 mmol) in 20 ml MeOH and 10 ml H2O, under reflux conditions for 20 hours and gave after evaporation, and co-evaporation with toluene, (R)-8-fluoro-5-carboxy-3-(N-3-pentyl-N-n-propylamino)chroman as a white solid. SOCl2 (0.8 ml, 11 mmol) was added to a slurry of (R)-8-fluoro-5-carboxy-3-(N-3-pentyl-N-n-propylamino)chroman in 50 ml dry CH2Cl2 and 1 drop DMF (catalytic amount). After reflux for 2 hours, the slurry was evaporated, and the residue, dissolved in 10 ml dry THF was added dropwise to 35 ml ice-cooled conc. NH3 under stirring. The THF was evaporated after 2 hours and extraction with EtOAc×2, drying (Na2SO4) and evaporation gave 0.51 g of a crude product. Purification by flash chromatography with hexane:EtOAc:NH3, (60:40:0.5) gave 0.41 g of (R)-5-carbamoyl-8-fluoro-3-(N-3-pentyl-N-n-propylamino)chroman as light yellow crystals.

Workup

  1. customgave
  2. customafter evaporation, and co-evaporation with toluene, (R)-8-fluoro-5-carboxy-3-(N-3-pentyl-N-n-propylamino)chroman as a white solid
  3. temperatureAfter reflux for 2 hours
  4. customthe slurry was evaporated
  5. dissolutionthe residue, dissolved in 10 ml dry THF
  6. additionwas added dropwise to 35 ml ice-
  7. temperaturecooled conc. NH3
  8. customThe THF was evaporated after 2 hours
  9. extractionextraction with EtOAc×2
  10. customdrying
  11. custom(Na2SO4) and evaporation
  12. customgave 0.51 g of a crude product
  13. customPurification by flash chromatography with hexane

Sources & evidence

ORD record
ord-4ef6489c496c4c1691378df505ccfa94
Source dataset
uspto-grants-1997_07
Patent number
US05646309

Reaction notes

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