Hydrochloric Acid → 1-[4-Fluoro-3-(trifluoromethyl)benzoyl]azetidine

HRID 1964585Notes

Reaction equation

HRID 1964585 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].Cl.[NH:16]1[CH2:19][CH2:18][CH2:17]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl>ClCCl>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:16]2[CH2:19][CH2:18][CH2:17]2)=[O:8])=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 5222684-Fluoro-3-(trifluoromethyl)benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12308726Azetidine hydrochloride

Product 1

HCID 666816671-[4-Fluoro-3-(trifluoromethyl)benzoyl]azetidineYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Commercially available 4-fluoro-3-(trifluoromethyl)benzoic acid (230 mg, 1.10 mmol) was dissolved in dichloromethane (50 mL), and azetidine hydrochloride (120 mg, 1.28 mmol), HATU (550 mg, 1.45 mmol) and N,N-diisopropylethylamine (0.50 mL, 2.87 mmol) were added, followed by stirring at room temperature for 4 hours under nitrogen atmosphere. 0.5N hydrochloric acid (100 mL) was added, and extraction was carried out with dichloromethane (100 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=60%-80%) to afford the desired compound (211 mg, yield 78%) as a colorless liquid.

Workup

  1. extractionextraction
  2. washThe organic layer was washed with saturated brine
  3. dry with materialsubsequently dried over anhydrous magnesium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe resulting residue was purified
  6. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=60%-80%)

Sources & evidence

ORD record
ord-8b74a11592264a1d824d4612737c2549
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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