Chlorotrimethylsilane → 2-[(2-Fluorophenyl)carbamoyl]acetic acid

HRID 418592Notes

Reaction equation

HRID 418592 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH2:8].C[Si](Cl)(C)C.CC1(C)[O:20][C:19](=O)[CH2:18][C:17](=[O:22])[O:16]1>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:19](=[O:20])[CH2:18][C:17]([OH:22])=[O:16]

Participants

5

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 95842-FluoroanilineHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dione

Product 1

HCID 164811562-[(2-Fluorophenyl)carbamoyl]acetic acidYield 26%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-fluorobenzeneamine (1 mL, 7.80 mmol) in DCM (78 mL) was added TMSCl (0.99 mL, 7.80 mmol) at RT [Rigo, B.; Fasseur, D.; Cauliez, P. and Couturier, D. Tetrahedron Lett.; 30; 23; 1989; 3073-3076.]. The reaction mixture was stirred for 30 min then 2,2-dimethyl-1,3-dioxane-4,6-dione (1.12 g, 7.80 mmol) was added and the combined mixture was stirred overnight. The solvent was removed under reduced pressure and the residue was dissolved in NaHCO3 solution, which was washed with EtOAc. The organic phase was discarded and the aqueous phase was acidified with conc. HCl to pH˜3, extracted with EtOAc; extract was dried (anhydrous Na2SO4) and concentrated. The residue was purified by flash chromatography (eluent CHCl3/MeOH/AcOH 8:1:0.1) to afford the acid 29 (0.4 g, 26% yield) as a white solid. 1H NMR (DMSO-d6) δ (ppm): 12.67 (s, broad, 1H), 9.95 (s, 1H), 7.95 (m, 1H), 7.25 (m, 1H), 7.12 (m, 1H), 3.43 (s, 2H). MS (m/z): 198.0 (M+H).

Workup

  1. stirringthe combined mixture was stirred overnight
  2. customThe solvent was removed under reduced pressure
  3. dissolutionthe residue was dissolved in NaHCO3 solution
  4. washwhich was washed with EtOAc
  5. extractionextracted with EtOAc
  6. extractionextract
  7. dry with materialwas dried (anhydrous Na2SO4)
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography (eluent CHCl3/MeOH/AcOH 8:1:0.1)

Sources & evidence

ORD record
ord-d54fb70b18d54eb3a9ad2e53be00944a
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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