4-Methylmorpholine → Boc-D-Valine amide

To a stirred solution of Boc-D-Valine (25 g, 115 mMol) in THF (300 mL) at 0° C. was added N-Methylmorpholine (15 mL, 136 mMol) followed by the dropwise addition of isoButyl chloroformate (18 mL, 139 mMol) over 5 minutes. The reaction was stirred at 0° C. for 30 minutes after which a solution of 30 wt. % NH4OH (50 mL, 385 mMol) was quickly poured into the reaction. (Vigorous gas evolution was seen which subsided after a few minutes.) The reaction was allowed to warm to RT and stirred for 4 h. The reaction was concentrated under vacuum on the rotoevaporator to a volume which precipitated most of the product. The thick white slurry was diluted with an equal volume of water, filtered, rinsed with water, pressed dry then dried under vacuum to give the title compound (22.56 g, 91%) as a white solid: 1H NMR (400 MHz, CDCl3) δ 6.17 (br s, 1H), 5.75 (br s, 1H), 5.12 (d, 1H), 4.00 (app. t, 1H), 2.13 (m, 1H), 1.44 (s, 9H), 0.99 (d, 3H), 0.94 (d, 3H).

1. additionwas quickly poured into the reaction
2. custom(Vigorous gas evolution was seen which subsided after a few minutes.)
3. concentrationThe reaction was concentrated under vacuum on the rotoevaporator to a volume which
4. customprecipitated most of the product
5. additionThe thick white slurry was diluted with an equal volume of water
6. filtrationfiltered
7. washrinsed with water
8. custompressed dry
9. customthen dried under vacuum

ORD record

ord-401280ad02794846804341ae0481a1b2

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07166595B2