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

HRID 538343노트

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HRID 538343 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-9650b736a44b4d698290c66427da2218
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865712B2

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