4-Methylmorpholine → (S)-3-Boc-amino-1-diazo-3-phenyl-2-butanone

Temperature

-25 °C

A solution of N-[[(1,1-dimethylethyl)oxy]carbonyl]-L-phenylalanine (20.01 g., 75 mmol) in 150 mL of dry tetrahydrofuran was chilled to -25° C. and treated with N-methylmorpholine (8.3 mL, 75 mmol) and isobutylchloroformate (9.8 mL, 75 mmol) and then stirred at -25° C. for 10 minutes. The reaction mixture was then filtered into a flask containing a solution of diazomethane (prepared from 35.48 g., 240 mmol of N-methyl-N'-nitro-N-nitrosoguanidine) in 300 mL of anhydrous ether at -78° C. and then let warm to -5° C. and stirred overnight. The cold reaction mixture was then filtered and the filtrate was washed with water, saturated sodium bicarbonate, and brine. The organic layer was dried (MgSO4), filtered and concentrated in vacuo to yield a reddish brown oil. The oil was triturated with cold petroleum ether to yield 14.42 g. of a light tan solid. The mother liquors were concentrated and allowed to stand yielding a second crop of 1.96 g. of light yellow crystals for a total yield of 16.38 g. of the title A compound as a tannish solid; m.p. 87°-90° C. [α]D =-32.2° (c=1.15, methanol).

1. filtrationThe reaction mixture was then filtered into a flask
2. temperaturelet warm to -5° C.
3. stirringstirred overnight
4. customThe cold reaction mixture
5. filtrationwas then filtered
6. washthe filtrate was washed with water, saturated sodium bicarbonate, and brine
7. dry with materialThe organic layer was dried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto yield a reddish brown oil
11. customThe oil was triturated with cold petroleum ether
12. customto yield 14.42 g
13. concentrationThe mother liquors were concentrated
14. customto stand yielding a second crop of 1.96 g

ORD record

ord-7d8e39d4020d4a3891cce6ef445e7172

Source dataset

uspto-grants-1995_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05414013