Sodium Bicarbonate → (2R,4R)-4-Azido-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 244349노트

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HRID 244349 반응식
[BH4-].[Li+].C[O:4][C:5]([C@H:7]1[CH2:11][C@@H:10]([N:12]=[N+:13]=[N-:14])[CH2:9][N:8]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=O.C(=O)(O)[O-].[Na+]>CCOCC>[C:18]([O:17][C:15]([N:8]1[CH2:9][C@H:10]([N:12]=[N+:13]=[N-:14])[CH2:11][C@@H:7]1[CH2:5][OH:4])=[O:16])([CH3:21])([CH3:20])[CH3:19]

참가 물질

5

반응물 3

HCID 516892Sodium BicarbonateHCID 4148881Lithium borohydrideHCID 585644271-tert-butyl 2-methyl (2R,4R)-4-azidopyrrolidine-1,2-dicarboxylate

생성물 1

HCID 58564434(2R,4R)-4-Azido-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester수율 96.4%

시약·촉매·용매 1

HCID 3283Diethyl Ether용매

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온도
-70 °C

실험 절차

Add lithium borohydride (8.50 g, 351 mmol) to a solution of (2R,4R)-4-azido-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (95 g, 351 mmol) in ether (1 L) at −30° C. under nitrogen. Allow the temperature to rise to 0° C. over 1.5 h and stir for an additional 2 h. Cool to −70° C. and add saturated aqueous sodium bicarbonate (1 L) dropwise. Allow to warm to room temperature, separate the layers and extract the aqueous layer with ether (1 L). Combine the ether layers, dry over sodium sulfate, filter, and concentrate. Dry the resulting material under high vacuum to obtain a yellow oil (82 g, 96%). [α]D20+20.3 (c=1.0 in methanol). 1H NMR (400 MHz, DMSO-d6) δ 1.38 (s, 9H), 1.99 (br s, 1H, OH), 2.20 (m, 1H), 3.34 (m, 1H), 3.50-3.78 (m, 1H), 4.29 (m, 1H), 4.78 (m, 1H).

후처리

  1. temperatureto warm to room temperature
  2. customseparate the layers
  3. extractionextract the aqueous layer with ether (1 L)
  4. dry with materialCombine the ether layers, dry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customDry the resulting material under high vacuum

출처 및 근거

ORD 기록
ord-a166316af83d415ea0c7f72ca0c595a8
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658638B2

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