1-Bromo-3-chlorobenzene → Di-tert-butyl 1-(2-bromo-6-chlorophenyl)hydrazine-1,2-dicarboxylate

Temperature

-78 °C

To a stirred solution of 2.5 M Butyllithium in hexanes (13.79 mL, 34.47 mmol) at −20° C. was added dropwise 2,2,6,6-tetramethylpiperidine (5.82 mL, 34.47 mmol) in THF (30 mL). This was stirred for 30 minutes. This solution was cooled down to −78° C., and a solution of 1-bromo-3-chlorobenzene (6 g, 31.34 mmol) in THF (20 mL) was added dropwise so as to maintain the temperature at <−70° C. After 2 hours (Z)-di-tert-butyl diazene-1,2-dicarboxylate (10.82 g, 47.01 mmol) in THF (30 mL) added dropwise at −78° C. Stirred at this temperature for 2 hours, then allowed to warm to room temperature overnight. Water (150 mL) added. The mixture was extracted with EtOAc (2×300 mL). The extracts were combined, washed with brine (100 mL), dried (MgSO4) and reduced go give a residue which was purified by flash silica chromatography, elution gradient 0-10% EtOAc in hexane. Fractions containing suspected product were combined, and reduced to give di-tert-butyl 1-(2-bromo-6-chlorophenyl)hydrazine-1,2-dicarboxylate (9.59 g, 72.5%) 1H NMR (400 MHz, DMSO) δ 1.30-1.50 (18H, s), 7.28 (1H, m), 7.55 (1H, dd), 7.67 (1H, dd), 9.18 (1H, s). m/z (ES+) (M+Na)+=443; HPLC tR=10.76 min.

1. temperatureto maintain the temperature at <−70° C
2. stirringStirred at this temperature for 2 hours
3. temperatureto warm to room temperature overnight
4. extractionThe mixture was extracted with EtOAc (2×300 mL)
5. washwashed with brine (100 mL)
6. dry with materialdried (MgSO4)
7. customreduced go give a residue which
8. customwas purified by flash silica chromatography, elution gradient 0-10% EtOAc in hexane
9. additionFractions containing suspected product

ORD record

ord-9210863cfc884525ba6c919fdff7d0fb

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08143263B2