Acetic Acid → Sitagliptin Phosphate Monohydrate

HRID 1261629ノート

反応式

HRID 1261629 の反応式
[O:1]=[C:2]([N:24]1[CH2:29][CH2:28][N:27]2[C:30]([C:33]([F:36])([F:35])[F:34])=[N:31][N:32]=[C:26]2[CH2:25]1)[CH2:3][C@H:4]([NH:15][C@@H](C1C=CC=CC=1)C)[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([F:13])=[CH:8][C:7]=1[F:14].C(O)(=[O:39])C.[H][H].[P:43](=[O:47])([OH:46])([OH:45])[OH:44]>CO.[Pd]>[CH:11]1[C:6]([CH2:5][C@@H:4]([NH2:15])[CH2:3][C:2]([N:24]2[CH2:25][C:26]3=[N:32][N:31]=[C:30]([C:33]([F:36])([F:35])[F:34])[N:27]3[CH2:28][CH2:29]2)=[O:1])=[C:7]([F:14])[CH:8]=[C:9]([F:13])[C:10]=1[F:12].[OH2:39].[OH:45][P:43]([OH:47])([OH:46])=[O:44]

参加物

7

反応物 4

HCID 176Acetic AcidHCID 1004Phosphoric AcidHCID 51001609(R)-3-[(R)-1-Phenylethylamino]-1-[3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazine-7-yl]-4-(2,4,5-trifluorophenyl)-1-butanoneHCID 178418361HCID 178418361、化合物

生成物 1

HCID 11591741Sitagliptin Phosphate Monohydrate収率 81.5%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 887Methanol溶媒

反応条件

温度
5 °C

実験手順

(2R)-4-oxo-N-[(1R)-1-phenylethyl]-1-(2,4,5-trifluorophenyl)-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]butan-2-amine [F] (25 g, 0.049 mol) was subjected to hydrogenolysis in methanol (75 ml) containing acetic acid (3.0 ml, 0.052 mol) using 5% palladium on charcoal as catalyst at 52±2° C. at hydrogen pressure of 2.0±0.5 kg/cm2. After completion on reaction the catalyst was removed by filtration and reaction mass was concentrated under vacuum. Obtained residue was suspended in water and pH was set to 10.0±0.4 with solution of potassium carbonate. Product was extracted into dichloromethane. The extract was concentrated and degassed. The obtained syrupy mass was dissolved in ethanol, phosphoric acid (3.5 ml, 0.060 mol) was added and the solution refluxed for 30 min. Cooled to 5±3° C., filtered the solid and dried to obtain 20.9 g sitagliptin phosphate, chromatographic purity was 99.8%; chiral purity (determined by chiral HPLC) was 100%.

後処理

  1. customat 52±2° C.
  2. customAfter completion on reaction the catalyst
  3. customwas removed by filtration and reaction mass
  4. concentrationwas concentrated under vacuum
  5. extractionProduct was extracted into dichloromethane
  6. concentrationThe extract was concentrated
  7. customdegassed
  8. dissolutionThe obtained syrupy mass was dissolved in ethanol
  9. temperaturethe solution refluxed for 30 min
  10. filtrationfiltered the solid
  11. customdried

出典と根拠

ORDレコード
ord-df33ff095e67401c818d894384035882
出典データセット
uspto-grants-2013_06
特許番号
US08471016B2

反応ノート

読み込み中…