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

HRID 1487302ノート

反応式

HRID 1487302 の反応式
[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]

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
85 °C

実験手順

(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+).

後処理

  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

出典と根拠

ORDレコード
ord-43c4fbb9a2564785b61e22675a9895ee
出典データセット
uspto-grants-2016_08
特許番号
US09428511B2

反応ノート

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