Tert-Butylamine → HCID 178449075, compound

Participants

Reaction Conditions

Reaction Steps

Set up a 1 L three neck round bottom flask fitted with a mechanical stirrer, temperature controller, addition funnel, and heating mantle. Suspend Trans-4-[[(5S)-5-[[[3,5-bis(trifluoromethyl)phenyl]methyl](2-methyl-2H-tetrazol-5-yl)amino]-2,3,4,5-tetrahydro-7,9-dimethyl-1H-1-benzazepin-1-yl]methyl]-cyclohexanecarboxylic acid hydrate (50 g) in heptane (500 mL). Heat the slurry to 69.1° C. and add tert-butylamine (5.57 g) as a solution in isopropyl alcohol (70 mL) and rinse in with 5 mL additional isopropyl alcohol. A solution forms immediately upon addition. During addition, temperature drops to 63° C. but heats back up to 69° C. once addition is complete. Seed with a spatula tip of Trans-4-[[(5S)-5-[[[3,5-bis(trifluoromethyl)phenyl]methyl](2-methyl-2H-tetrazol-5-yl)amino]-2,3,4,5-tetrahydro-7,9-dimethyl-1H-1-benzazepin-1-yl]methyl]-cyclohexanecarboxylic acid tert-butylamine. A suspension begins to form—continue stirring at 69° C. Begin cooling the reaction to 55° C. In about an hour, a thick slurry forms. Continue cooling to 45° C. In about an hour, bring temperature of slurry down to 35° C. In about 2 hours, remove heat source and allow to cool to ambient temperature. In about 3 hours, filter the slurry (temperature is now 21° C.) and rinse with 100 mL of heptane. Dry using a vacuum for about an 1.5 hours. Dry over the weekend in vacuo at 33° C. This results in 55.9 g. The XRD spectrum was collected as described in Example 7. Table 4 below lists the peaks obtained from the XRD spectrum.

Provenance & Evidence