Potassium Hydroxide → Ammonia

HRID 1684302ノート

反応式

HRID 1684302 の反応式
[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]

参加物

10

反応物 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

生成物 2

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

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide触媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

(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.

後処理

  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

出典と根拠

ORDレコード
ord-45eb5328dc3546d8b622a4ec5461a9b2
出典データセット
uspto-grants-1997_06
特許番号
US05639784

反応ノート

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