Lithium Hexamethyldisilazide → 3-(4-Bromo-6-methyl-1H-indazol-1-yl)benzoic acid

HRID 1925592Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4](Br)[C:3]=1[CH:10]=[N:11][NH:12][C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=1)[C:16]([OH:18])=[O:17].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>CN(C=O)C>[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]2[C:3]=1[CH:10]=[N:11][N:12]2[C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=1)[C:16]([OH:18])=[O:17]

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 3-{2-[(2,6-dibromo-4-methylphenyl)methylidene]hydrazino}benzoic acid (1050 g) in DMF (3.46 L) was cooled to 10° C. under nitrogen. Lithium bis(trimethylsilyl)amide solution (1M in THF, 6.34 L) was then added while maintaining the temperature below 15° C. The stirred solution was heated at 70±3° C. for 64 hrs and then the reaction mixture was cooled to 5° C. and quenched sequentially with the slow addition of water (4.2 L), 5M hydrochloric acid (2.62 L) and water (3.68 L). The resulting slurry was stirred at 5° C. for 1 hr 34 min, filtered and washed successively with purified water (1 L and then 2.1 L at 5±5° C.) and methanol (2×1 L at 5±5° C.). The solid was dried in vacuo at 50° C. to afford the title compound (742.9 g).

Workup

temperaturewhile maintaining the temperature below 15° C
temperaturethe reaction mixture was cooled to 5° C.
customquenched sequentially with the slow addition of water (4.2 L), 5M hydrochloric acid (2.62 L) and water (3.68 L)
filtrationfiltered
washwashed successively with purified water (1 L
customat 5±5° C.
custommethanol (2×1 L at 5±5° C.)
customThe solid was dried in vacuo at 50° C.

Sources & evidence

ORD record: ord-26cdd1dc04644fc4880c2bb7d1310145
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178573B2

Reaction notes

Loading…