Potassium Carbonate → 2-Fluoromethoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzaldehyde

HRID 1065978Notes

Reaction equation

HRID 1065978 reaction equation
Cl[CH2:2][F:3].[OH:4][C:5]1[CH:12]=[CH:11][C:10]([N:13]2[C:17]([C:18]([F:21])([F:20])[F:19])=[N:16][N:15]=[N:14]2)=[CH:9][C:6]=1[CH:7]=[O:8].C(=O)([O-])[O-].[K+].[K+].[Br-].[Na+]>O.CN(C=O)C>[F:3][CH2:2][O:4][C:5]1[CH:12]=[CH:11][C:10]([N:13]2[C:17]([C:18]([F:21])([F:20])[F:19])=[N:16][N:15]=[N:14]2)=[CH:9][C:6]=1[CH:7]=[O:8]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 11643ChlorofluoromethaneHCID 253881Sodium BromideHCID 112769072-Hydroxy-5-(5-trifluoromethyl-tetrazol-1-yl)benzaldehyde

Product 1

HCID 211972442-Fluoromethoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzaldehyde

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-78 °C

Procedure

A 500 mL nitrogen purged round bottom flask fitted with a dry-ice condenser was cooled to −78° C. and 50 mL (ca. 40 g by cylinder difference) of chlorofluoromethane was condensed. DMF (200 mL), 2-hydroxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzaldehyde (40 g, 0.155 mol), powdered potassium carbonate (22 g, 0.159 mol, 1.03 equiv) and sodium bromide (22 g, 0.21 mol) were carefully added. An additional 100 mL of DMF was added and the dry-ice bath was removed. The pale yellow suspension was warmed first to room temperature, then to 70-75° C. (oil bath). Gentle reflux was noted. After 3 h, an additional 30 g of NaBr was added. The condenser was kept cold for ca. 10 h and allowed to warm to room temperature overnight. The white suspension which resulted was diluted with 2 L of water and extracted with ether (1×1 L, 2×500 mL). The combined extracts were washed with water (4×250 mL) and brine (500 mL), dried with magnesium sulfate, filtered and the filtrate concentrated. During concentration the product began to crystallize. The filtrare was concentrated to a small volume and the mixture flushed with hexanes. The resulting slurry was cooled to 0° C., aged 1 hr, filtered, and the cake washed with hexanes. The yield upon drying was 42.2 g (93.8%) of white crystalline 2-fluoromethoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzaldehyde: 1H NMR (CDCI3) δ 5.91 (d, JH-F=30.5 Hz, 2H), 7.47 (d, J=9 Hz, 1H), 7.72 (dd, J=9, 2.7 Hz, 1H), 8.02 (d, J=2.7 Hz, 1H), 10.49 (s, 1H). MS (EI) m/z 290. Anal. Calcd for C10H6F4N4O2: C, 41.39; H, 2.08; F, 26.19; N, 19.31. Found: C, 41.39; H, 1.98; F, 25.79; N, 19.53.

Workup

  1. customA 500 mL nitrogen purged round bottom flask fitted with a dry-ice condenser
  2. customcondensed
  3. customthe dry-ice bath was removed
  4. temperatureThe pale yellow suspension was warmed first to room temperature
  5. customto 70-75° C.
  6. temperatureGentle reflux
  7. additionan additional 30 g of NaBr was added
  8. waitThe condenser was kept cold for ca. 10 h
  9. temperatureto warm to room temperature overnight
  10. customThe white suspension which resulted
  11. extractionextracted with ether (1×1 L, 2×500 mL)
  12. washThe combined extracts were washed with water (4×250 mL) and brine (500 mL)
  13. dry with materialdried with magnesium sulfate
  14. filtrationfiltered
  15. concentrationthe filtrate concentrated
  16. concentrationDuring concentration the product
  17. customto crystallize
  18. concentrationThe filtrare was concentrated to a small volume
  19. customthe mixture flushed with hexanes
  20. temperatureThe resulting slurry was cooled to 0° C., aged 1 hr
  21. filtrationfiltered
  22. washthe cake washed with hexanes
  23. customThe yield
  24. customupon drying

Sources & evidence

ORD record
ord-f25e0b6ead04418baea52b69a05e8485
Source dataset
uspto-grants-2001_06
Patent number
US06241964B1

Reaction notes

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