Thioglycolic Acid → (2S,4S)-4-Acetylthio-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

HRID 37344

반응식

HRID 37344 반응식
O[C@H:2]1[CH2:6][N:5]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)=[O:8])[C@H:4]([C:20]([N:22]2[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][O:30][C:31]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=3)=[O:32])[CH2:24][CH2:23]2)=[O:21])[CH2:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC([O:67][CH2:68][CH3:69])=O.[SH:75]CC(O)=O>O1CCCC1>[C:68]([S:75][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)=[O:8])[C@H:4]([C:20]([N:22]2[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][O:30][C:31]([O:33][CH2:34][C:35]3[CH:36]=[CH:37][C:38]([N+:41]([O-:43])=[O:42])=[CH:39][CH:40]=3)=[O:32])[CH2:24][CH2:23]2)=[O:21])[CH2:3]1)(=[O:67])[CH3:69]

참가 물질

6

반응물 4

HCID 1133Thioglycolic AcidHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 22881632(2S,4R)-4-hydroxy-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinyl carbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

생성물 1

HCID 57136373(2S,4S)-4-Acetylthio-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine수율 77.6%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

실험 절차

105 g of (2S,4R)-4-hydroxy-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (prepared as described in Preparation 15) and 55 g of triphenylphosphine were dissolved in 700 ml of tetrahydrofuran, and a solution of 36.5 g of diethyl azodicarboxylate in 100 ml of tetrahydrofuran was added dropwise to it, whilst ice-cooling. The resulting mixture was then stirred at the same temperature for 10 minutes. At the end of this time, a solution of 15.9 g of mercaptoacetic acid in 100 ml of tetrahydrofuran was added dropwise to the mixture, and the resulting mixture was stirred at room temperature for 1 hour., The mixture was then concentrated by evaporation under reduced pressure. The concentrate was dissolved in 1.5 liters of ethyl acetate and washed with water and with an aqueous solution of sodium chloride, in that order. The organic layer was dried over anhydrous sodium sulfate and then concentrated by evaporation under reduced pressure. The resulting residue was mixed with 400 ml of diisopropyl ether and a soluble material was removed. This procedure was repeated four times in all. The residue was subjected to column chromatography through 3 kg of silica gel using mixtures of ethyl acetate and methanol ranging from 1:0 to 20:1 by volume as the eluent. Those fractions containing the title compound were collected and concentrated by evaporation under reduced pressure, to afford 88.4 g of the title compound as a colorless powder.

후처리

  1. temperaturecooling
  2. stirringthe resulting mixture was stirred at room temperature for 1 hour
  3. concentration, The mixture was then concentrated by evaporation under reduced pressure
  4. dissolutionThe concentrate was dissolved in 1.5 liters of ethyl acetate
  5. washwashed with water and with an aqueous solution of sodium chloride, in that order
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. concentrationconcentrated by evaporation under reduced pressure
  8. additionThe resulting residue was mixed with 400 ml of diisopropyl ether
  9. customa soluble material was removed
  10. additionThose fractions containing the title compound
  11. customwere collected
  12. concentrationconcentrated by evaporation under reduced pressure

출처 및 근거

ORD 기록
ord-405c59a71e524b93a1be5e5b750a81da
출처 데이터셋
uspto-grants-1995_05
특허 번호
US05420119

연결된 노트

불러오는 중…