二碳酸二叔丁酯 → (S)-3-(Boc-amino)-4,4-dimethyldihydrofuran-2(3H)-one

HRID 520352笔记

反应方程式

HRID 520352 反应方程式
[N:1]([C@H:4]1[C:8]([CH3:10])([CH3:9])[CH2:7][O:6][C:5]1=[O:11])=[N+]=[N-].[O:12](C(OC(C)(C)C)=O)[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=O>CO.C(Cl)Cl.CCOC(C)=O.[Pd]>[CH3:9][C:8]1([CH3:10])[CH2:7][O:6][C:5](=[O:11])[C@H:4]1[NH:1][C:13](=[O:12])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17]

参与物

7

反应物 2

HCID 90495二碳酸二叔丁酯HCID 10057735(S)-3-Azido-4,4-dimethyldihydrofuran-2(3H)-one

产物 1

HCID 10331393(S)-3-(Boc-amino)-4,4-dimethyldihydrofuran-2(3H)-one

试剂、催化剂与溶剂 4

HCID 23938钯碳催化剂HCID 887(5BETA,17BETA)-17-羟基-17-(甲基-D3)-2'H-雄甾-2-烯并[3,2-C]吡唑-5'(1'H)-酮溶剂HCID 6344二氯甲烷溶剂HCID 8857乙酸乙酯溶剂

实验过程

To a solution of (S)-3-azido-4,4-dimethyldihydrofuran-2(3H)-one (5.52 g) in MeOH 910 mL) was added 10% Pd/C (0.379 g, 0.356 mmol) under N2. The reaction mixture was stirred under H2 at rt for 16 hrs. The reaction was filtered through diatomaceous earth (Celite®), washed with EtOAc and the filtrate was concentrated to yield a clear oil. To the above oil in DCM (10 mL) was added BOC2O (9.09 mL) and TEA (13.88 mL). The reaction mixture was stirred at rt for 16 hrs. The reaction mixture was diluted with EtOAc, washed with sat. NaHCO3, citric acid, water, sat. NaCl, dried over anhydrous Na2SO4, filtered and concentrated to yield an oil. The crude product was purified by silica gel chromatography (0-100% EtOAc in hexane) to yield (S)-tert-butyl 4,4-dimethyl-2-oxotetrahydrofuran-3-ylcarbamate (3.8 g) as a white solid. LC/MS (Cond. N-1): [M+Na]+ 252.06, RT=2.75 min. 1H NMR (400 MHz, CHLOROFORM-d) ppm 4.81-4.95 (1H, m), 4.38 (1H, d, J=7.78 Hz), 3.97-4.07 (2H, m), 1.47 (9H, s), 1.25 (3H, s), 1.01 (3H, s).

后处理

  1. filtrationThe reaction was filtered through diatomaceous earth (Celite®)
  2. washwashed with EtOAc
  3. concentrationthe filtrate was concentrated
  4. customto yield a clear oil
  5. stirringThe reaction mixture was stirred at rt for 16 hrs
  6. washwashed with sat. NaHCO3, citric acid, water, sat. NaCl
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto yield an oil
  11. customThe crude product was purified by silica gel chromatography (0-100% EtOAc in hexane)

来源与证据

ORD记录
ord-2500128def064324a78f9ab3b52dfdd6
来源数据集
uspto-grants-2016_05
专利号
US09326973B2

反应笔记

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