4-Toluenesulfonyl chloride → (3S,4R)-benzyl 3-methyl-4-(tosyloxy)pyrrolidine-1-carboxylate

HRID 1487301노트

반응식

HRID 1487301 반응식
[OH:1][C@@H:2]1[C@@H:6]([CH3:7])[CH2:5][N:4]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:3]1.[S:18](Cl)([C:21]1[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=1)(=[O:20])=[O:19]>N1C=CC=CC=1>[CH3:7][C@@H:6]1[C@@H:2]([O:1][S:18]([C:21]2[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=2)(=[O:20])=[O:19])[CH2:3][N:4]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:5]1

참가 물질

4

반응물 2

HCID 73974-Toluenesulfonyl chlorideHCID 58277753benzyl (3R,4S)-3-hydroxy-4-methylpyrrolidine-1-carboxylate

생성물 1

HCID 86707891(3S,4R)-benzyl 3-methyl-4-(tosyloxy)pyrrolidine-1-carboxylate수율 92.8%

시약·촉매·용매 1

HCID 1049Pyridine용매

실험 절차

(3R,4S)-Benzyl 3-hydroxy-4-methylpyrrolidine-1-carboxylate (19.6 g, 83 mmol) was dissolved in pyridine (83 ml). To the above solution, Ts-Cl (22.2 g, 117 mmol) was added in portions at rt. After overnight stirring, the reaction mixture was concentrated in vacuo to remove pyridine. The residue was quenched with ice water (200 mL), extracted with ethyl acetate (3×150 mL). The combined ethyl acetate phase was washed with water, 1N HCl, water and sat. NaHCO3, then dried with Na2SO4. After concentration, (3S,4R)-benzyl 3-methyl-4-(tosyloxy)pyrrolidine-1-carboxylate (30 g, 92% yield) was obtained as light yellow oil. 1H NMR (400 MHz, chloroform-d) δ ppm 7.76-7.83 (2H, m), 7.30-7.40 (7H, m), 5.11 (2H, s), 4.57-4.64 (1H, m), 3.56-3.73 (2H, m), 3.38-3.54 (1H, m), 3.08-3.19 (1H, m), 2.33-2.55 (4H, m), 0.97 (3H, dd, J=14.86, 7.15 Hz); LCMS (CHROMOLITH® RP-18e 2.0×50 mm, 0.8 mL/min, Solvent A: 10% MeOH/water with 0.1% TFA, Solvent B: 90% MeOH/water with 0.1% TFA, gradient with 0-100% B over 4 minutes) retention time: 3.60 min; MS(ES+) m/z: 390 (M+H+).

후처리

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customto remove pyridine
  3. customThe residue was quenched with ice water (200 mL)
  4. extractionextracted with ethyl acetate (3×150 mL)
  5. washThe combined ethyl acetate phase was washed with water, 1N HCl, water and sat. NaHCO3
  6. dry with materialdried with Na2SO4
  7. concentrationAfter concentration

출처 및 근거

ORD 기록
ord-95ffff329ea94338ae11a981d3d1d20a
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09428511B2

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