Formaldehyde → HCID 67607739, compound

Temperature

2.5 °C

Anhydrous methanol (10 ml) was charged in a dry round bottom flask at 20-25° C. under nitrogen atmosphere. 2-amino-6-chloro-benzoic acid (201 mg, 1.17 mmol) was added, followed by paraformaldehyde (351.1 mg, 1.17 mmol). The mixture was stirred and cooled to 0-5° C. A 30 wt % solution of sodium methoxide (0.975 ml, 5.26 mmol) was added dropwise, keeping the temperature at 0-5° C. while stirring. The mixture was allowed to warm to room temperate (r.t.). Then, the resulting solution was heated to reflux for 1.5 h, then cooled to r.t. Sodium borohydride (209.1 mg, 5.5 mmol) was added in one portion, and the resulting mixture was heated to reflux for 2 h, then cooled to r.t. The reaction was concentrated by removal of solvent under reduced pressure. Chloroform (30 ml) and DM water (20 ml) were added, the mixture was cooled to 0-5° C., and the pH was adjusted to pH=2-3 with 1N HCl while stirring. The organic phase was separated and kept aside. The extraction step with chloroform (30 ml) was repeated twice more, the organic phases were combined and dried over sodium sulfate. The solvent was removed under reduced pressure resulting in a yellowish solid. Yield: 80%. The purity of the isolated product (Intermediate I-A) was 97% (HPLC, area %).

1. customat 0-5° C.
2. stirringwhile stirring
3. temperatureto warm to room temperate (r.t.)
4. temperatureThen, the resulting solution was heated
5. temperatureto reflux for 1.5 h
6. temperaturecooled to r.t
7. temperaturethe resulting mixture was heated
8. temperatureto reflux for 2 h
9. temperaturecooled to r.t
10. concentrationThe reaction was concentrated by removal of solvent under reduced pressure
11. additionChloroform (30 ml) and DM water (20 ml) were added
12. temperaturethe mixture was cooled to 0-5° C.
13. stirringwhile stirring
14. customThe organic phase was separated
15. extractionThe extraction step with chloroform (30 ml)
16. dry with materialdried over sodium sulfate
17. customThe solvent was removed under reduced pressure
18. customresulting in a yellowish solid

ORD record

ord-916ab842ca934354a31f5fb05e5629b7

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09102592B2