Potassium Hydroxide → Ammonia

HRID 1684092노트

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HRID 1684092 반응식
[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]

참가 물질

10

반응물 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

생성물 2

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

시약·촉매·용매 4

HCID 6228Dimethylformamide촉매HCID 887Methanol용매HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

(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.

후처리

  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

출처 및 근거

ORD 기록
ord-f279e1e28e034366a032936cf9c43028
출처 데이터셋
uspto-grants-1997_06
특허 번호
US05639772

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