Hydrochloric Acid → ethyl 6-chloro-5-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 855033노트

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HRID 855033 반응식
[Cl:1][C:2]1[C:3]([F:11])=[C:4]([C:7]([OH:10])=[CH:8][CH:9]=1)[CH:5]=O.C(=O)([O-])[O-].[K+].[K+].[F:18][C:19]([F:28])([F:27])/[CH:20]=[CH:21]/[C:22]([O:24][CH2:25][CH3:26])=[O:23].Cl>CN(C=O)C>[Cl:1][C:2]1[C:3]([F:11])=[C:4]2[C:7](=[CH:8][CH:9]=1)[O:10][CH:20]([C:19]([F:18])([F:28])[F:27])[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:5]2

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 5371261Ethyl (2E)-4,4,4-trifluoro-2-butenoate2회HCID 589347903-Chloro-2-fluoro-6-hydroxybenzaldehyde

생성물 1

HCID 58934464ethyl 6-chloro-5-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
70 °C

실험 절차

To 1.1 g (6.7 mmole) of 3-chloro-2-fluoro-6-hydroxybenzaldehyde in 2 mL DMF was added 1.0 g (7.2 mmole) of potassium carbonate and 3A molecular sieves. The stirred mixture was heated to 70° C. and treated with 1.5 mL (1.69 g, 10.0 mmole) of ethyl 4,4,4-trifluorocrotonate. After lh the mixture was treated with an additional 1.5 mL of ethyl 4,4,4-trifluorocrotonate and allowed to react overnight. To the cooled mixture was added 1N HCl, the mixture extracted three times with methylene chloride and the combined organic fractions dried and concd. The resultant oil was dissolved in ether, washed three times with water and concd to give an oil. Chromatographic purification (silica, 5-10% EtOAc/hex) gave 0.76 g (35%) of a clear, yellow oil: 1H NMR (CDCl3/400 MHz) 1.37 (t, 3H, J=7.2 Hz), 4.34 (m, 2H), 5.72 (q, 1H, J=6.8 Hz), 6.77 (d, 1H, J=8.8 Hz), 7.32 (t, 1H, J=8.5 Hz), 7.92 (s, 1H); 19F NMR (CDCl3/400 MHz) −78.7 (d, 3F, J=6.8 Hz), −119.6 (d, 1F, J=7.7 Hz); 13C NMR (CDCl3/100 MHz) 14.2, 61.9, 70.8 (q, J=33.4 Hz), 110.0 (d, J=18.1 Hz), 112.6 (d, J=4.0 Hz), 114.4 (d, J=17.3 Hz), 118.2 (J=2.3 Hz), 123.2 (q, J=287.3 Hz), 129.2 (d, J=4.6 Hz), 133.2 (d, J=1.3 Hz), 152.2 (d, J=4.4 Hz), 154.9 (d, J=256.4 Hz), 163.3; MS (ESI+) 325 (M+l, 100); MS (EI) 324 (M+, 21), 255 (100), 227 (83); HRMS (EI) m/z calcd for (C13H9O3ClF4) 324.0176, found 324.0171.

후처리

  1. customto react overnight
  2. extractionthe mixture extracted three times with methylene chloride
  3. customthe combined organic fractions dried
  4. dissolutionThe resultant oil was dissolved in ether
  5. washwashed three times with water and concd
  6. customto give an oil
  7. customChromatographic purification (silica, 5-10% EtOAc/hex)
  8. customgave 0.76 g (35%) of a clear, yellow oil

출처 및 근거

ORD 기록
ord-d3f1587307e9434eb04d9733b3f8c3c6
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07259266B2

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