Ammonia → Methyl 3,4-dichloro-5-methoxybenzoate

Temperature

65 °C

A suspension of copper (II) chloride (0.97 g, 7.2 mmol) and tert-butyl nitrite (1.07 mL, 9.04 mmol) in anhydrous MeCN (5 mL) was warmed to 65° C. A solution of methyl 3-amino-4-chloro-5-methoxybenzoate (4) (1.3 g, 6.0 mmol) in anhydrous MeCN (3 mL) was added dropwise. Once the addition was complete the mixture was allowed to cool to RT and poured on to 1M HCl (15 mL). The acidic mixture was neutralized with satd. NaHCO3 solution and aq. ammonia (35%, 5 mL) was added. The product was extracted with DCM (25 mL) and then washed with aq. ammonia (17.5%, 20 mL) and brine (2×20 mL). The solvent was removed in vacuo and the residue was triturated with 10% EtOAc in isohexane to afford methyl 3,4-dichloro-5-methoxybenzoate (5) (1.17 g, 79% yield) as a brown solid: 1H NMR (400 MHz, DMSO-d6) δ: 7.72 (1H, d), 7.57 (1H, d), 3.98 (3H, s), 3.89 (3H, s).

1. additionOnce the addition
2. temperatureto cool to RT
3. extractionThe product was extracted with DCM (25 mL)
4. washwashed with aq. ammonia (17.5%, 20 mL) and brine (2×20 mL)
5. customThe solvent was removed in vacuo
6. customthe residue was triturated with 10% EtOAc in isohexane

ORD record

ord-9e5deb272bdc4bdf821f95dd2b873987

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09447028B2