Sodium Azide → (3S,4S)-benzyl 3-azido-4-methylpyrrolidine-1-carboxylate

HRID 1487302노트

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HRID 1487302 반응식
[CH3:1][C@@H:2]1[C@@H:6](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:5][N:4]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:3]1.[N-:28]=[N+:29]=[N-:30].[Na+]>CN(C=O)C>[N:28]([C@H:6]1[C@@H:2]([CH3:1])[CH2:3][N:4]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:5]1)=[N+:29]=[N-:30]

참가 물질

4

반응물 2

HCID 33557Sodium AzideHCID 86707891(3S,4R)-benzyl 3-methyl-4-(tosyloxy)pyrrolidine-1-carboxylate

생성물 1

HCID 86707890(3S,4S)-benzyl 3-azido-4-methylpyrrolidine-1-carboxylate수율 97.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
85 °C

실험 절차

(3S,4R)-Benzyl 3-methyl-4-(tosyloxy)pyrrolidine-1-carboxylate (20 g, 51.4 mmol) was dissolved in DMF (42.8 ml). Sodium azide (5.68 g, 87 mmol) was added at rt and heated up to 85° C. overnight. LCMS shows a complete conversion. The reaction mixture was cooled to rt, quenched with ice water, extracted with ethyl acetate. Organic phases were combined, washed with water, brine, then dried with Na2SO4. After concentration, (3S,4S)-benzyl 3-azido-4-methylpyrrolidine-1-carboxylate (13 g, 97% yield) was obtained as a yellowish oil and used directly for the next reduction. 1H NMR (400 MHz, chloroform-d) δ ppm 7.29-7.44 (5H, m), 5.08-5.22 (2H, m), 3.94-4.04 (1H, m), 3.52-3.76 (3H, m), 3.00-3.15 (1H, m), 2.29-2.48 (1H, m), 1.13 (3H, t, J=7.04 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: 3.41 min; MS(ES+) m/z: 261.0 (M+H+).

후처리

  1. temperatureThe reaction mixture was cooled to rt
  2. customquenched with ice water
  3. extractionextracted with ethyl acetate
  4. washwashed with water, brine
  5. dry with materialdried with Na2SO4
  6. concentrationAfter concentration

출처 및 근거

ORD 기록
ord-43c4fbb9a2564785b61e22675a9895ee
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09428511B2

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