Hydrochloric Acid → HCID 178500727, compound

Temperature

20 °C

To the solution of formamidine acetate (1.05 eq) in methanol (5 vol) was added 29.2% NaOMe/methanol (3 eq) at 0° C. for 0.25 h and the mixture was stirred for 0.5 h. To this was added the mixture of (R)-trimethyl 2-methylpropane-1,1,3-tricarboxylate (1.1 kg, 20 L) and methanol (50% w/w) for 0.5 h. After warming to 20° C., the reaction mixture was stirred for 14 h. The reaction mixture was neutralized with 5% aq HCl at 0° C. When pH was about 7, the mixture was concentrated. To the mixture was added methanol (0.7 vol), the mixture was washed with MTBE (5 vol), acidified with HCl to pH about 2 at 2° C., and stirred for 1 h at 60° C. After cooling to 0° C., the mixture was filtered and the cake was washed with water (1 vol) and dried in vacuum at 50° C. to get the product as solid (0.8 kg, 66% yield, 96% purity).

1. additionTo this was added
2. stirringthe reaction mixture was stirred for 14 h
3. concentrationWhen pH was about 7, the mixture was concentrated
4. additionTo the mixture was added methanol (0.7 vol)
5. washthe mixture was washed with MTBE (5 vol)
6. customacidified with HCl to pH about 2 at 2° C.
7. stirringstirred for 1 h at 60° C
8. temperatureAfter cooling to 0° C.
9. filtrationthe mixture was filtered
10. washthe cake was washed with water (1 vol)
11. customdried in vacuum at 50° C.

ORD record

ord-965b869d2e4444ab8a7f0b0cc31874be

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309204B2