5-Bromo-2-methoxypyridine → HCID 118276731、化合物

HRID 530645ノート

反応式

HRID 530645 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C([Li])(C)(C)C.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][O:25][C@H:24]([C:28](=[O:33])N(OC)C)[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>C1(C)C=CC=CC=1>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][O:25][C@H:24]([C:28]([C:2]2[CH:7]=[N:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=2)=[O:33])[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

参加物

5

反応物 3

HCID 27348955-Bromo-2-methoxypyridineHCID 591669901,1-Dimethylethyl (2S)-2-[(methoxymethylamino)carbonyl]-4-morpholinecarboxylateHCID 178418306HCID 178418306、化合物

生成物 1

HCID 118276731HCID 118276731、化合物収率 89.6%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

反応条件

温度
-75 °C

実験手順

5-Bromo-2-methoxypyridine (247 mg, 1.31 mmol) was dissolved in toluene (6 mL) and cooled to −75° C. t-Butyl lithium (0.77 mL of 1.7 M in pentane, 1.3 mmol) was added dropwise. Stirring was continued at the same temperature for 15 min and then in an ice bath for 5 min. The reaction was cooled to −75° C. and a solution of (S)-2-(methoxy-methyl-carbamoyl)-morpholine-4-carboxylic acid tert-butyl ester (300 mg, 1.09 mmol) in toluene (3 mL) was added dropwise over 5 min. The reaction was stirred at 0° C. for 1.25 h and then poured onto water. The mixture was extracted 3 times with ethyl acetate. The combined organic phase was washed with brine, dried over MgSO4 and concentrated. The crude product was purified by flash chromatography (1:1 EtOAc/heptane eluent) to afford (S)-2-(6-methoxy-pyridine-3-carbonyl)-morpholine-4-carboxylic acid tert-butyl ester (315 mg, 89%) as a colorless oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.49 (s, 9H) 2.97-3.25 (m, 2H) 3.63-3.76 (m, 1H) 3.85-3.97 (m, 1H) 4.02 (s and overlapping m, 4H) 4.10-4.32 (m, 1H) 4.50-4.66 (m, 1H) 6.80 (dd, J=8.87, 0.54 Hz, 1H) 8.17 (dd, J=8.87, 2.42 Hz, 1H) 8.91 (d, J=2.42 Hz, 1H).

後処理

  1. additionwas added dropwise
  2. waitin an ice bath for 5 min
  3. stirringThe reaction was stirred at 0° C. for 1.25 h
  4. additionpoured onto water
  5. extractionThe mixture was extracted 3 times with ethyl acetate
  6. washThe combined organic phase was washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography (1:1 EtOAc/heptane eluent)

出典と根拠

ORDレコード
ord-c87b112245a04a5e97d3ba30e85edb5e
出典データセット
uspto-grants-2016_05
特許番号
US09353096B2

反応ノート

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