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

HRID 855033ノート

反応式

HRID 855033 の反応式
[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

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 5371261Ethyl (2E)-4,4,4-trifluoro-2-butenoate2 回HCID 589347903-Chloro-2-fluoro-6-hydroxybenzaldehyde

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
70 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-d3f1587307e9434eb04d9733b3f8c3c6
出典データセット
uspto-grants-2007_08
特許番号
US07259266B2

反応ノート

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