Triethylamine → Methanesulfonic acid 2-azido-1-(2-bromo-5-fluoro-pyridin-4-yl)-1-methyl-ethyl ester

HRID 538343ノート

反応式

HRID 538343 の反応式
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[N:6]([CH2:9][C:10]([C:13]1[C:18]([F:19])=[CH:17][N:16]=[C:15]([Br:20])[CH:14]=1)([OH:12])[CH3:11])=[N+:7]=[N-:8].CCN(CC)CC>C(Cl)Cl>[N:6]([CH2:9][C:10]([O:12][S:2]([CH3:1])(=[O:4])=[O:3])([C:13]1[C:18]([F:19])=[CH:17][N:16]=[C:15]([Br:20])[CH:14]=1)[CH3:11])=[N+:7]=[N-:8]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 866680521-Azido-2-(2-bromo-5-fluoro-pyridin-4-yl)-propan-2-ol

生成物 1

HCID 86668053Methanesulfonic acid 2-azido-1-(2-bromo-5-fluoro-pyridin-4-yl)-1-methyl-ethyl ester

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

At 0° C., methanesulfonyl chloride (2.04 ml, 3.00 g, 26.20 mmol) was dropwise added to a solution of 1-azido-2-(2-bromo-5-fluoro-pyridin-4-yl)-propan-2-ol (6.00 g, 21.81 mmol) and NEt3 (3.65 ml, 2.65 g, 26.2 mmol) in DCM (200 ml). The reaction mixture was stirred at 0° C. for 1 h, then for another 1 h at 0° C. to rt. The reaction mixture was quenched with 1M aq. NaHCO3 soln. and diluted with DCM. The phases were separated and the aq. phase was twice reextracted with DCM. The combined org. phases were dried over Na2SO4, filtered and concentrated. HPLC purification (Alltech Grom Saphir 65 Si 10 μM column, 250×50 mm, gradient n-heptane:EtOAc 0-1.6 min 85:15, 1.6-16 min 0:100, 16-21.2 min 0:100, flow 100 ml/min, detection 254 nm) yielded the title compound as well as recovered starting material that could be reacted again according to the above procedure. HPLC RtH4=0.96 min; ESIMS: 353, 355 [(M+H)+]; 1H NMR (400 MHz, CDCl3): b 8.28 (d, 1H), 7.56 (d, 1H), 4.08 (d, 1H), 3.82 (d, 1H), 3.22 (s, 3H), 2.13 (s, 3H).

後処理

  1. waitfor another 1 h at 0° C. to rt
  2. customThe reaction mixture was quenched with 1M aq. NaHCO3 soln
  3. additionand diluted with DCM
  4. customThe phases were separated
  5. dry with materialphases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customHPLC purification (Alltech Grom Saphir 65 Si 10 μM column, 250×50 mm, gradient n-heptane:EtOAc 0-1.6 min 85:15, 1.6-16 min 0:100, 16-21.2 min 0:100, flow 100 ml/min, detection 254 nm)

出典と根拠

ORDレコード
ord-9650b736a44b4d698290c66427da2218
出典データセット
uspto-grants-2014_10
特許番号
US08865712B2

反応ノート

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