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

HRID 861658ノート

反応式

HRID 861658 の反応式
[OH:1][C@H:2]1[CH2:6][NH:5][C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1.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:5]1[CH2:6][C@H:2]([OH:1])[CH2:3][C@H:4]1[C:7]([OH:9])=[O:8])([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]

参加物

6

反応物 3

HCID 5810L-HydroxyprolineHCID 516892Sodium BicarbonateHCID 14261773Fluorenylmethyl chloroformate

生成物 1

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

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 218864351,4-Dioxane--water (1/1)溶媒

実験手順

trans-4-Hydroxy-L-proline (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) δ 7.75-7.15 (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).

後処理

  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

出典と根拠

ORDレコード
ord-118a945870284902a81d4571b572b5af
出典データセット
uspto-grants-1998_02
特許番号
US05714606

反応ノート

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