Hydrochloric Acid → 1,2,4-Pyrrolidinetricarboxylic acid, 1-(1,1-dimethylethyl) 2,4-dimethyl ester, (2S,4S)-

HRID 1509659노트

반응식

HRID 1509659 반응식
[C:1]([C@@H:3]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:5]([C:15]([O:17][CH3:18])=[O:16])[CH2:4]1)#N.Cl.[C:20](OC(OC(C)(C)C)=O)(OC(C)(C)C)=[O:21].C[OH:36]>>[N:6]1([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:7][C@@H:3]([C:1]([O:21][CH3:20])=[O:36])[CH2:4][C@H:5]1[C:15]([O:17][CH3:18])=[O:16]

참가 물질

5

반응물 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 90495Di-tert-butyl dicarbonateHCID 177504541,2-Pyrrolidinedicarboxylic acid, 4-cyano-, 1-(1,1-dimethylethyl) 2-methyl ester, (2S,4S)-

생성물 1

HCID 108508301,2,4-Pyrrolidinetricarboxylic acid, 1-(1,1-dimethylethyl) 2,4-dimethyl ester, (2S,4S)-수율 94%

실험 절차

To a solution of (2S,4S)-1-tert-butyl 2-methyl 4-cyanopyrrolidine-1,2-dicarboxylate (9.0 g, 35.4 mmol) in MeOH (196 mL) was added HCl (4M in 1,4-dioxane, 100 mL, 403 mmol). The solution was stirred at room temperature for 16h and concentrated in vacuo. The crude intermediate was dissolved in EtOAc (180 mL) and basified with aqueous bicarbonate (sat.). Di-tert-butyl dicarbonate (8.5 g, 38.9 mmol) was added and the biphasic solution was stirred at room temperature for 12h. The layers were then separated and the aqueous layer was backextracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The crude oil was purified by silica gel chromatography (15% to 40% to 100% EtOAc/Hexanes) to provide (2S,4S)-1-tert-butyl 2,4-dimethyl pyrrolidine-1,2,4-tricarboxylate (9.56 g, 94%).

후처리

  1. concentrationconcentrated in vacuo
  2. dissolutionThe crude intermediate was dissolved in EtOAc (180 mL)
  3. customThe layers were then separated
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude oil was purified by silica gel chromatography (15% to 40% to 100% EtOAc/Hexanes)

출처 및 근거

ORD 기록
ord-b0b69ff99f844f4181fc166bf205bee4
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221833B2

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