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

HRID 474080노트

반응식

HRID 474080 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-f45fdd0c97aa4091ac7bfe492f65d452
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637508B2

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