2,5-Dibromopyridine → 3-(5-Bromo-pyridine-2-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 423393

反応式

HRID 423393 の反応式
[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][N:8]=1.[C:14]([O:18][C:19]([N:21]1[CH2:25][CH2:24][CH:23]([C:26](=[O:31])N(OC)C)[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]>C1(C)C=CC=CC=1>[C:14]([O:18][C:19]([N:21]1[CH2:25][CH2:24][CH:23]([C:26]([C:7]2[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][N:8]=2)=[O:31])[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]

参加物

5

反応物 3

HCID 693532,5-DibromopyridineHCID 57419605Tert-butyl 3-[methoxy(methyl)carbamoyl]pyrrolidine-1-carboxylateHCID 178418339Butyllithium

生成物 1

HCID 666738453-(5-Bromo-pyridine-2-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester収率 43%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

反応条件

温度
-80 °C

実験手順

Add dropwise n-BuLi (3.2 mL, 5.1 mmol) to an suspension of 2,5-dibromopyridine (1.0 g, 4.2 mmol) in dry toluene (50 mL) at −80° C. under nitrogen. Allow the mixture to stir at −80° C. for 2 h. Slowly add a solution of 3-(methoxy-methyl-carbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.4 g, 5.5 mmol) in dry toluene (10 mL). Allow the reaction mixture to stir for 1 h at −78° C., then warm to −10° C. Quench the mixture with saturated NH4Cl (1 mL) and warm to RT. Separate the organic layer and concentrate. Purify the crude material by flash chromatography, eluting with 10-20% ethylacetate/hexane to give 0.61 g (43%) of the title compound. LC-MS/ES m/z (79Br) 299 [M-tert-Bu+H]+.

後処理

  1. stirringto stir for 1 h at −78° C.
  2. temperaturewarm to −10° C
  3. customQuench the mixture with saturated NH4Cl (1 mL)
  4. temperaturewarm to RT
  5. customSeparate the organic layer
  6. concentrationconcentrate
  7. customPurify the crude material by flash chromatography
  8. washeluting with 10-20% ethylacetate/hexane

出典と根拠

ORDレコード
ord-43c18ff452f74b25851cdba05be5e396
出典データセット
uspto-grants-2012_01
特許番号
US08101764B2

関連ノート

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