Formamidine acetate → HCID 178500110, compound

Participants

Reaction Conditions

Reaction Steps

A 12-L, 4-necked reactor, equipped with a mechanical stirrer, was charged with 2.80 L of methanol and sparged with nitrogen. The solvent was treated with NaOMe (1969 mL, 8612 mmol) and transfer washed with 250 mL of methanol. The mixture was left to stir for 1.5 hours before the solution was treated with formamidine acetate (246.6 g, 2368 mmol) in one sum (granular-homogenized). The mixture was allowed to stir for 20 minutes (the solids dissolved within about 10 minutes post addition) to afford a homogeneous solution. Trimethyl 2-methylpropane-1,1,3-tricarboxylate (500 g, 2153 mmol) was added via dropping funnel as a solution in 500 mL of methanol over a five minute period, followed by 200 mL more of methanol to complete transfer. The reaction (clear, bright yellow) was allowed to stir at ambient temperature overnight to completion as measured by NMR analysis (alliquot of 250 uL was removed via pipet and treated with five drops of aq. 3N HCl, reduced under vacuum to dryness, dissolved in d6-DMSO and then filtered) after 16 hours. The reaction was placed in an ice-bath and cooled to about 3.1° C. over a one hour period. A three-pound bottle of HCl (g) was used to quench the reaction (bubbling gas into solution via teflon tubing) over a one hour ten minute period reaching an endpoint of about pH=2.5 (via paper). The temperature was maintained below about 9.6° C. throughout the addition, and the yellow solution changed to an off-white suspension. The suspension was concentrated using vacuum distillation (35-37° C. @ 200 Torr) of the methanol (removed 3.34 L) in vacuo to afford a white/tan paste. The mixture was suspended in 3.75 L of toluene (7.5× volume) and stirred for 30 minutes. The suspension was filtered off (table top filter/polypropylene cloth, pad washed with 2×500 mL portions of toluene). The pad of product was allowed to air-dry under suction overnight on the filter then broken up with a spatula to give 396.8 grams, 86.9% yield.

Provenance & Evidence