Triethylamine → ethyl 5-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 855136Notes

Reaction equation

HRID 855136 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([OH:10])[C:3]=1[CH:4]=O.[F:11][C:12]([F:21])([F:20])/[CH:13]=[CH:14]/[C:15]([O:17][CH2:18][CH3:19])=[O:16].C(N(CC)CC)C.C(=O)([O-])[O-].[K+].[K+]>Cl>[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:3]=1[CH:4]=[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:13]([C:12]([F:11])([F:21])[F:20])[O:10]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 27373276-FluorosalicylaldehydeHCID 5371261Ethyl (2E)-4,4,4-trifluoro-2-butenoate2×

Product 1

HCID 58934554ethyl 5-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylateYield 62.2%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A mixture of 8.7 g (62 mmole) of 2-fluoro-6-hydroxybenzaldehyde, 18.6 mL (20.9 g, 124 mmole) of ethyl trifluorocrotonate and 17.3 mL (12.6 g, 124 mmole) of triethylamine was heated to reflux. After 3 hrs an additional 18.6 mL of ethyl trifluorocrotonate and 2 g of potassium carbonate was added and the mixture heated for 3 days. The mixture was allowed to cool, concd in vacuo, diluted with 1N HCl and extracted three times with diethyl ether. The combined extracts were washed with 1N HCl, brine, dried and concd to afford a dark oil. Kugelrohr distillation (0.2 torr, 50° C.) afforded 11.2 g (62%) of a white solid: mp 45.5-47.0° C.; 1H NMR (CDCl3/400 MHz) 1.33 (t, 3H, J=7.1 Hz), 4.30 (m, 2H), 5.68 (q, 1H, J=6.8 Hz), 6.70 (t, 1H, J=9.0 Hz), 6.76 (d, 1H, J=8.3 Hz), 7.24 (q, 1H, J=7.2 Hz), 7.92 (s, 1H); 19F NMR (CDCl3/ 400 MHz) −78.9 (d, 3F, J=7.7 Hz), −118.9 (m, 1F); 13C NMR (CDCl3/100 MHz) 14.2, 61.6, 70.7 (q, J=33.2 Hz), 108.7 (d, J=18.7 Hz), 109.2 (d, CH, J=20.6 Hz), 111.9 (d, CH, J=3.2 Hz), 117.0, 123.3 (q, J=287.5 Hz), 129.9 (d, CH, J=5.0 Hz), 133.2 (d, CH, J=10.3 Hz), 153.9, 158.5, 162.3 (d, J=253.5 Hz); MS(ES+) 291 (M+1, 100); MS(EI) 290 (M+, 13), 245 (18), 221 (100), 193 (99); HRMS (EI) m/z calcd for (C13H10O3F4) 290.0566, found 290.0589.

Workup

  1. temperaturewas heated to reflux
  2. temperaturethe mixture heated for 3 days
  3. temperatureto cool
  4. extractionextracted three times with diethyl ether
  5. washThe combined extracts were washed with 1N HCl, brine
  6. customdried
  7. customto afford a dark oil
  8. distillationKugelrohr distillation (0.2 torr, 50° C.)

Sources & evidence

ORD record
ord-d6d98864f9094d1fbda46720df95ee34
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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