Hydrochloric Acid → 5-Bromo-6-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acid

HRID 624947노트

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HRID 624947 반응식
Cl[C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][C:3]=1[Br:11].CC(C)([O-])C.[K+].[F:18][C:19]([F:26])([C:22]([F:25])([F:24])[F:23])[CH2:20][OH:21].Cl>CN(C=O)C.C1COCC1>[Br:11][C:3]1[CH:4]=[CH:5][C:6]([C:8]([OH:10])=[O:9])=[N:7][C:2]=1[O:21][CH2:20][C:19]([F:26])([F:18])[C:22]([F:25])([F:24])[F:23]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 98722,2,3,3,3-PentafluoropropanolHCID 23665647Potassium tert-butoxideHCID 446077145-Bromo-6-chloropicolinic acid

생성물 1

HCID 866747855-Bromo-6-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acid수율 22%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

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온도
140 °C

실험 절차

To a solution of 6-chloro-5-bromo-pyridine-2-carboxylic acid (CAN 959958-25-9, 1.7 g, 7.19 mmol) in DMF (90 mL) and THF (30 mL) was added potassium tert-butoxide (2.02 g, 18.0 mmol) and 2,2,3,3,3-pentafluoropropan-1-ol (5.73 mL, 57.5 mmol). The mixture was stirred at 140° C. for 4 days, cooled and poured into ice-water (100 mL). 2 M Hydrochloric acid (15 mL) was added to adjust the pH to 2-3 and the mixture was extracted with TBME, organic layers were washed twice with water, pooled, dried with Na2SO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, ethyl acetate/n-heptane gradient) to give the title compound (548 mg, 22%) as light-brown solid; LC-MS (UV peak area, ESI) 100%, 347.9306 [M−H−].

후처리

  1. temperaturecooled
  2. extractionthe mixture was extracted with TBME, organic layers
  3. washwere washed twice with water
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, ethyl acetate/n-heptane gradient)

출처 및 근거

ORD 기록
ord-d68ba1923fc0461798d28d9c00cef0c1
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09303012B2

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