Benzoyl fluoride → 1-(3,3,3-Trifluoro-2-(methylamino)propyl)azetidin-3-yl benzoate

HRID 1808812Notes

Reaction equation

HRID 1808812 reaction equation
[C:1](F)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:10][C:11]([F:22])([F:21])[CH:12]([NH:19][CH3:20])[CH2:13][N:14]1[CH2:17][CH:16]([OH:18])[CH2:15]1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:1]([O:18][CH:16]1[CH2:15][N:14]([CH2:13][CH:12]([NH:19][CH3:20])[C:11]([F:10])([F:21])[F:22])[CH2:17]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 67999Benzoyl fluorideHCID 516892Sodium BicarbonateHCID 677731291-(3,3,3-Trifluoro-2-(methylamino)propyl)azetidin-3-ol

Product 1

HCID 677729361-(3,3,3-Trifluoro-2-(methylamino)propyl)azetidin-3-yl benzoateYield 44.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of benzoyl fluoride (1.37 mL, 12.6 mmol) in DCM (5 mL) was added dropwise under argon to an ice cooled solution of 1-(3,3,3-trifluoro-2-(methylamino)propyl)azetidin-3-ol (Compound C3.1) (2.28 g, 11.5 mmol) and TEA (3.21 mL, 23 mmol) in DCM (45 mL). The stirring was continued at rt for 2.5 h. NaHCO3 (saturated, 20 mL) was added and the mixture was stirred vigorously for 40 min. The layers were separated, the aqueous layer was extracted with DCM, and the combined organic layers were washed with NaHCO3 (saturated), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by preparative HPLC. After concentrating the fractions to approximately 30 mL the aqueous emulsion was extracted DCM (×2). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure to give the title product (1.54 g, 44%.) as a colourless oil. 1H NMR (500 MHz, DMSO-d6) δ 7.97 (2H), 7.67 (1H), 7.53 (2H), 5.16 (1H), 3.7-3.79 (2H), 3.25 (1H), 3.18 (1H), 2.92-3.02 (1H), 2.66 (1H), 2.59 (1H), 2.38 (3H), 1.99-2.06 (1H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with DCM
  3. washthe combined organic layers were washed with NaHCO3 (saturated)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by preparative HPLC
  7. concentrationAfter concentrating the fractions to approximately 30 mL the aqueous emulsion
  8. extractionwas extracted DCM (×2)
  9. dry with materialThe combined organic layers were dried (Na2SO4)
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-04da266fb2c4496bafcc49cc2b1796f4
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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