4-Fluorobenzoyl chloride → HCID 56846694, compound

HRID 1529573Notes

Reaction equation

HRID 1529573 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.[O:11]([CH2:18][C:19]1[O:20][C:21]2[CH2:22][NH:23][CH2:24][CH2:25][C:26]=2[N:27]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C(Cl)Cl.C([O-])(O)=O.[Na+]>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:23]2[CH2:24][CH2:25][C:26]3[N:27]=[C:19]([CH2:18][O:11][C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)[O:20][C:21]=3[CH2:22]2)=[O:7])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 678794-Fluorobenzoyl chlorideHCID 66609262HCID 66609262, compound

Product 1

HCID 56846694HCID 56846694, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

4-Fluorobenzoyl chloride (0.25 mL, 2.12 mmol) was added dropwise to a stirred solution of 4,5,6,7-tetrahydro-2-(phenoxymethyl)-oxazolo[5,4-c]pyridine (0.37 g, 1.63 mmol) and TEA (0.34 mL, 2.44 mmol) in DCM (8.15 mL) at 0° C. The reaction mixture was stirred at room temperature for 15 minutes and then diluted with a saturated solution of NaHCO3. The organic layer was separated, dried (Na2SO4), filtered and the solvent evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 30/70). The desired fractions were collected and the solvents evaporated in vacuo. The crude product was triturated with heptane to yield 5-(4-fluorobenzoyl)-4,5,6,7-tetrahydro-2-(phenoxymethyl)-oxazolo[5,4-c]pyridine (0.38 g, 67% yield) as a white solid. C20H17FN2O3. 1H NMR (400 MHz, CDCl3) δ ppm 2.73 (br. s., 2 H), 3.69 (br. s., 1.4 H), 3.99 (br. s., 0.6 H), 4.57 (br. s., 0.6 H), 4.78 (br. s., 1.4 H), 5.12 (br. s., 2 H), 7.02 (d, J=7.4 Hz, 3 H), 7.14 (t, J=8.6 Hz, 2 H), 7.31 (t, J=7.7 Hz, 2 H), 7.43-7.51 (m, 2 H).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. customthe solvent evaporated in vacuo
  5. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 30/70)
  6. customThe desired fractions were collected
  7. customthe solvents evaporated in vacuo
  8. customThe crude product was triturated with heptane

Sources & evidence

ORD record
ord-ef774a5b9a534a8794ce91ab8374fadb
Source dataset
uspto-grants-2015_07
Patent number
US09090632B2

Reaction notes

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