Reaktion #90992

Reaktionsgleichung

methyl 4-aminobenzoate

DIPEA

3,5-dichloro-4-(cyclopentyloxy)benzoic acid

3,5-Dichloro-4-(cyclopentyloxy)benzoic acid

oxalyl chloride

→

methyl 4-(3,5-dichloro-4-(cyclopentyloxy)benzamido)benzoate

Ausbeute 20.2%

Lösungsmittel

DMF

DCM

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solvent was evaporated in vacuo
2. 2
   workup.DISSOLUTIONthe residue dissolved in DCM (5 mL)
3. 3
   Sonstigepartitioned between DCM (20 mL) and aqueous HCl (20 mL, 1 M)
4. 4
   SonstigeThe phases were separated
5. 5
   Waschenthe organic phase was washed successively with water (2×20 mL), and brine (20 mL)
6. 6
   Trocknendried over MgSO4
7. 7
   Filtrationfiltered
8. 8
   Sonstigethe solvent was removed in vacuo
9. 9
   SonstigeThe residue was purified by silica gel chromatography (12 g, 0-100% EtOAc in isohexane)

Vorschrift

A solution of 3,5-dichloro-4-(cyclopentyloxy)benzoic acid (3) (100 mg, 363 μmol) in DCM (5 mL), cooled to 0° C., was treated with oxalyl chloride (63.6 μL, 727 μmol), followed by a drop of DMF. The resultant mixture was stirred for 1 h at RT. The solvent was evaporated in vacuo and the residue dissolved in DCM (5 mL), and then treated with a solution of methyl 4-aminobenzoate (54.9 mg, 363 μmol) and DIPEA (190 μL, 1.09 mmol) in DCM (5 mL). The reaction mixture was stirred for 12 h at RT and then partitioned between DCM (20 mL) and aqueous HCl (20 mL, 1 M). The phases were separated and the organic phase was washed successively with water (2×20 mL), and brine (20 mL), dried over MgSO4, filtered and then the solvent was removed in vacuo. The residue was purified by silica gel chromatography (12 g, 0-100% EtOAc in isohexane) to afford methyl 4-(3,5-dichloro-4-(cyclopentyloxy)benzamido)benzoate (AAA-002) (30 mg, 20%): m/z 406 (M−H)− (ES−). NMR (400 MHz, CDCl3) δ: 8.06 (2H, d), 7.85 (1H, br s), 7.82 (2H, s), 7.71 (2H, d), 5.05 (1H, m), 3.92 (3H, s), 2.10-1.90 (4H, m), 1.85-1.70 (2H, m), 1.70-1.60 (2H, m).

Quelle