Citric Acid → 4-Amino-5-chloro-2-methoxybenzaldehyde

Temperature

0 °C

Isopropylmagnesium chloride (2M in tetrahydrofuran, 23 ml, 46 mmol) (commercially available, for example, from Aldrich) was added over 5 minutes to a stirred solution of 4-bromo-2-chloro-5-methoxyaniline (Step A) (10 g, 42 mmol) in tetrahydrofuran (70 ml) at −10° C. The resulting solution was allowed to warm to 0° C. over 50 minutes to give a thick slurry, then cooled to −25° C. and n-butyllithium (1.6M in hexanes, 90 ml, 144 mmol) was added over 20 minutes followed by tetrahydrofuran (20 ml). The solution was warmed to −10° C. over 30 minutes and then N,N-dimethylformamide (16 ml, 207 mmol) was added over 5 minutes and the resulting thick slurry was warmed to 0° C. over 20 minutes. A solution of citric acid (22 g, 105 mmol) in water (50 ml) was added cautiously over 15 minutes keeping reaction at <10° C. The slurry was aged at 20° C. for 30 minutes then filtered under vacuum. The cake was washed with water (100 ml) and then dried under vacuum at 40° C. for 16 hours to give 4-amino-5-chloro-2-methoxybenzaldehyde (6.1 g, 80% th) as a pale yellow solid.

1. customto give a thick slurry
2. temperaturecooled to −25° C.
3. temperatureThe solution was warmed to −10° C. over 30 minutes
4. temperaturethe resulting thick slurry was warmed to 0° C. over 20 minutes
5. customreaction at <10° C
6. filtrationthen filtered under vacuum
7. washThe cake was washed with water (100 ml)
8. customdried under vacuum at 40° C. for 16 hours

ORD record

ord-2b043ebcde994cbfb82cc95a9141afc2

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08519138B2