L-Hydroxyproline → (2S,4R)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-4-hydroxypyrrolidine-2-carboxylic acid

HRID 440450노트

반응식

HRID 440450 반응식
[NH:1]1[CH2:9][C@H:7]([OH:8])[CH2:6][C@H:2]1[C:3]([OH:5])=[O:4].C([O-])(O)=O.[Na+].Cl[C:16]([O:18][CH2:19][C:20]1[C:32]2[CH2:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24]=2[CH:23]=[CH:22][CH:21]=1)=[O:17]>O.O1CCOCC1.C1(C)C=CC=CC=1>[C:16]([N:1]1[CH2:9][C@H:7]([OH:8])[CH2:6][C@H:2]1[C:3]([OH:5])=[O:4])([O:18][CH2:19][CH:20]1[C:21]2[C:28](=[CH:29][CH:24]=[CH:23][CH:22]=2)[C:27]2[C:32]1=[CH:31][CH:30]=[CH:25][CH:26]=2)=[O:17]

참가 물질

6

반응물 3

HCID 5810L-HydroxyprolineHCID 516892Sodium BicarbonateHCID 14261773Fluorenylmethyl chloroformate

생성물 1

HCID 2756109(2S,4R)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-4-hydroxypyrrolidine-2-carboxylic acid

시약·촉매·용매 2

HCID 1140Toluene용매HCID 218864351,4-Dioxane--water (1/1)용매

실험 절차

Hydroxyproline, 1, (5.00 g, 38.2 mmol) and NaHCO3 (8.00 g, 95.2 mmol) were suspended in 150 ml H2O/Dioxane (1:1). Fluorenylmethyl chloroformate (11.4 g, 44.0 mmol) in 25 ml toluene was added dropwise. The temperature of the reaction was not allowed to rise above 25° C. during the addition. The mixture was stirred vigorously overnight, and then quenched with 50 ml saturated NaHCO3 solution and 50 ml water. The solution was then extracted with 100 ml diethyl ether. The aqueous layer was acidified to pH 1 with concentrated HCl, and extracted twice with ethyl acetate, and the organic extracts washed with brine. The solution was dried with MgSO4, filtered and the solvent removed in vacuo. The pure product crystallized from the concentrated solution. Yield: 13.4 g (100%). 1H NMR: (CDCl3, 200 MHz) δ7.75-7.15 (8H, m, ArH), 4.55-4.05 (5H, m, ArCHCH2, H2, H4), 3.65-3.45 (2H, m, 2 H5), 2.35-2.10 (2H, m, 2 H3).

후처리

  1. additionto rise above 25° C. during the addition
  2. customquenched with 50 ml saturated NaHCO3 solution and 50 ml water
  3. extractionThe solution was then extracted with 100 ml diethyl ether
  4. extractionextracted twice with ethyl acetate
  5. washthe organic extracts washed with brine
  6. dry with materialThe solution was dried with MgSO4
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. customThe pure product crystallized from the concentrated solution

출처 및 근거

ORD 기록
ord-d427a4102d664c899dfa4eff67b6c1a1
출처 데이터셋
uspto-grants-1996_05
특허 번호
US05519134

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