Triethylamine → Methanesulfonic acid 2-(2-bromo-5-fluoro-pyridin-4-yl)-2-hydroxy-propyl ester

HRID 474080ノート

反応式

HRID 474080 の反応式
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([OH:12])([CH3:11])[CH2:9][OH:10])[C:5]([F:13])=[CH:4][N:3]=1.C(N(CC)CC)C.[CH3:21][S:22](Cl)(=[O:24])=[O:23]>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[C:6]([C:8]([OH:12])([CH3:11])[CH2:9][O:10][S:22]([CH3:21])(=[O:24])=[O:23])[C:5]([F:13])=[CH:4][N:3]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 866680502-(2-Bromo-5-fluoro-pyridin-4-yl)-propane-1,2-diol

生成物 1

HCID 86668051Methanesulfonic acid 2-(2-bromo-5-fluoro-pyridin-4-yl)-2-hydroxy-propyl ester

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a suspension of 2-(2-bromo-5-fluoro-pyridin-4-yl)-propane-1,2-diol (17.45 g, 69.8 mmol) and triethylamine (19.45 ml, 14.12 g, 140 mmol) in DCM (350 ml) at 0° C. was added dropwise methanesulfonyl chloride (5.71 ml, 8.39 g, 73.3 mmol) over a period of 10 min. The reaction mixture was stirred at 0° C. for 30 min, then quenched with 1M aq. NaHCO3 soln. The phases were separated, the aq. phase was twice reextracted with DCM and the combined org. phases were washed with brine, dried over Na2SO4, filtered and concentrated. Flash chromatography on silica gel (gradient heptane: EtOAc 0-5 min 88:12, 5-37.5 min 24:76) yielded the title compound as a clear oil. HPLC RtH4=0.76 min; ESIMS: 328, 330 [(M+H)+]; 1H NMR (400 MHz, DMSO-d6): δ 8.22 (d, 1H), 7.82 (d, 1H), 4.58-4.47 (m, 2H), 3.04 (s, 3H), 3.00 (s, 1H), 1.64 (s, 3H).

後処理

  1. customquenched with 1M aq. NaHCO3 soln
  2. customThe phases were separated
  3. washphases were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-f45fdd0c97aa4091ac7bfe492f65d452
出典データセット
uspto-grants-2014_01
特許番号
US08637508B2

反応ノート

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