Trifluoroacetic acid → HCID 22718086, compound

HRID 2227722Notes

Reaction equation

HRID 2227722 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3[N:17]([CH2:18][CH2:19][OH:20])[N:16]=[CH:15][CH:14]=3)=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[O-:23][C:24]#[N:25].[Na+].FC(F)(F)C(O)=O>C1(C)C=CC=CC=1.C([O-])(O)=O.[Na+]>[C:24]([O:20][CH2:19][CH2:18][N:17]1[C:13]([C:10]2[CH:9]=[CH:8][C:7]([O:6][C:5]3[CH:21]=[CH:22][C:2]([F:1])=[CH:3][CH:4]=3)=[CH:12][CH:11]=2)=[CH:14][CH:15]=[N:16]1)(=[O:23])[NH2:25]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 517096Sodium CyanateHCID 22718119HCID 22718119, compound

Product 1

HCID 22718086HCID 22718086, compoundYield 15.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 2-[5-[4-(4-fluorophenoxy)phenyl]-pyrazol-1-yl]ethanol (118 mg, 0.40 mmol) in 1 mL of toluene was treated with solid sodium cyanate (2 eq.; 53 mg, 0.82 mmol) added in one portion. The resulting mixture was cooled in an ice-water bath and neat trifluoroacetic acid (60 μL, 89 mg, 0.78 mmol) was added dropwise via syringe. The reaction was stirred at room temperature. After 2 hours, the reaction had completely solidified and an additional 1 mL of toluene was added. After stirring overnight, the reaction was recooled to 0° C. and diluted with 3 mL of a saturated aqueous NaHCO3 solution. The aqueous layer was separated and extracted with EtOAc (3×5 mL). The organic layers were combined, washed with brine, dried (Na2SO4), filtered and concentrated. Column chromatography (13 cm of flash silica in a 2 cm diameter column eluted with 600 mL of 3:2 CH2Cl2/EtOAc) afforded 21 mg (15%) of the carbamate as a solid, mp 120-125° C. 1H NMR (CDCl3): δ7.57 (d, 1H, J=2 Hz), 7.35 (d, 2H, J=9 Hz), 7.10-7.05 (m, 4H), 7.02 (d, 2H, J=9 Hz), 6.26 (d, 1H, J=2 Hz), 4.60 (br s, 2H), 4.43 (t, 2H), 4.35 (t, 2H).

Workup

  1. additionadded in one portion
  2. temperatureThe resulting mixture was cooled in an ice-water bath
  3. stirringAfter stirring overnight
  4. customwas recooled to 0° C.
  5. customThe aqueous layer was separated
  6. extractionextracted with EtOAc (3×5 mL)
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. washColumn chromatography (13 cm of flash silica in a 2 cm diameter column eluted with 600 mL of 3:2 CH2Cl2/EtOAc)

Sources & evidence

ORD record
ord-40937b19378141a3a90c27a07d855a45
Source dataset
uspto-grants-2002_07
Patent number
US06414011B1

Reaction notes

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