Hydrochloric Acid → 4-nitrobenzyl (5R,6R)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-7-oxo-3-(3-pyridylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

HRID 235778

反応式

HRID 235778 の反応式
C(N(C(C)C)CC)(C)C.O=[C:11]1[CH2:17][C@H:16]2[N:13]([C:14](=[O:35])[C@H:15]2[C:18]([CH3:34])([O:20][C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)=[O:22])[CH3:19])[C@H:12]1[C:36]([O:38][CH2:39][C:40]1[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=1)=[O:37].FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.Cl.[SH:65][C:66]1[CH:67]=[N:68][CH:69]=[CH:70][CH:71]=1>ClCCl.CN(C1C=CN=CC=1)C.CN(C)C=O>[CH3:19][C:18]([C@@H:15]1[C:14](=[O:35])[N:13]2[C@@H:16]1[CH2:17][C:11]([S:65][C:66]1[CH:67]=[N:68][CH:69]=[CH:70][CH:71]=1)=[C:12]2[C:36]([O:38][CH2:39][C:40]1[CH:41]=[CH:42][C:43]([N+:46]([O-:48])=[O:47])=[CH:44][CH:45]=1)=[O:37])([O:20][C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=1)=[O:22])[CH3:34]

参加物

9

反応物 5

HCID 313Hydrochloric Acid2 回HCID 276913-Mercaptopyridine2 回HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531Diisopropylethylamine3 回HCID 185992114-nitrobenzyl (2R,5R,6R)-3,7-dioxo-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-1-azabicyclo[3.2.0]heptane-2-carboxylate

生成物 1

HCID 536341654-nitrobenzyl (5R,6R)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-7-oxo-3-(3-pyridylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate収率 55.4%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒2 回HCID 6344Dichloromethane溶媒3 回

反応条件

温度
-30 °C

実験手順

A solution of N,N-diisopropyl-N-ethylamine (0.579 ml) in dichloromethane (5.21 ml) was added to a solution of 4-nitrobenzyl (2R, 5R, 6R)-3,7-dioxo-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-1-azabicyclo[3.2.0]heptane-2-carboxylate (1.50 g) and 4-(N,N-dimethylamino)pyridine (33.8 mg) in dichloromethane (75.0 ml) at -30° C. To this solution was added a solution of trifluoromethanesulfonic anhydride (0.489 ml) in dichloromethane (9.29 ml) and the mixture was stirred at -30° C. for 20 minutes. N,N-Diisopropyl-N-ethylamine (5.31 ml) and a solution of stannic chloride and hydrochloric acid salts of 3-mercaptopyridine (1.70 g) in N,N-dimethylformamide (15.3 ml) were then added to the mixture and the resultant mixture was allowed to warm to 20° C. over a period of 3 hours. After cooling to 0° C., additional N,N-diisopropyl-N-ethylamine (2.89 ml) and a solution of stannic chloride and hydrochloric acid salts of 3-mercaptopyridine (0.570 g) in N,N-dimethylformamide (5.13 ml) were added to the mixture. The resultant mixture was allowed to warm to 20° C. over a period of an hour and evaporated in vacuo. The residue was dissolved in dichloromethane (250 ml), washed in turn with cold water (x6) and an aqueous sodium chloride, dried over magnesium sulfate, and evaporated in vacuo. The residue was chromatographed on deactivated silica gel with 15% water (150 g), eluting with a mixture of benzene and acetone (50:1 to 8:1). Crystallization from a mixture of dichloromethane and diethyl ether gave 4 -nitrobenzyl (5R,6R)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-7-oxo-3-(3-pyridylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (0.9747 g). The mother liquor was purified by column chromatography on silica gel, followed by crystallization to give the same product (0.2680 g) as a pale yellow powder. Total yield is 1.2427 g.

後処理

  1. temperatureto warm to 20° C. over a period of 3 hours
  2. temperatureAfter cooling to 0° C.
  3. temperatureto warm to 20° C. over a period of an hour
  4. customevaporated in vacuo
  5. dissolutionThe residue was dissolved in dichloromethane (250 ml)
  6. washwashed in turn with cold water (x6)
  7. dry with materialan aqueous sodium chloride, dried over magnesium sulfate
  8. customevaporated in vacuo
  9. customThe residue was chromatographed on deactivated silica gel with 15% water (150 g)
  10. washeluting with a mixture of benzene and acetone (50:1 to 8:1)
  11. customCrystallization
  12. additionfrom a mixture of dichloromethane and diethyl ether

出典と根拠

ORDレコード
ord-19dfff13e2b9441282d351a2f89c5500
出典データセット
uspto-grants-1987_02
特許番号
US04640915

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