Yield:-

Reaction Conditions:

with thionyl chloride at 2 - 40; for 17.5 h;

Steps:

21

Intermediate 21; methyl (2R)-2-[(tert-butoxycarbonyl)amino]-2-methylpent-4-ynoate (2R)-2-amino-2-methylpent-4-ynoic acid (1.3 kg) was suspended in methanol (6.5 L) and cooled to 2+/-3° C. The mixture was treated with thionyl chloride (1.48 L) at 2+/-3° C. over at least 30 mins. The mixture was heated at 40+/-3° C. for at least 17 hours then sampled for completion of reaction (COR) by ¹H NMR. Once complete, the mixture was stripped to low volume (ca. 1 vol) then azeotroped with toluene (ca. 2×2.5 L) and evaporated to dryness to afford crude methyl (2R)-2-amino-2-methylpent-4-ynoate which was then diluted with dioxane (9.1 L).

References:

US2009/286836,2009,A1 Location in patent:Page/Page column 26