Chloroacetyl chloride → HCID 68955176, compound

Temperature

0 °C

Add triethylamine (7.0 mL, 50.6 mmol) to a RT slurry of (S)-2-amino-3-benzyloxy-propan-1-ol hydrochloride (5 g, 23.0 mmol) in CH2Cl2 (75 mL). Stir until all the solid dissolves and then cool to 0° C. Add chloroacetylchloride (2.0 mL, 25.3 mmol). Stir 1 h and add more TEA (960 μL, 6.9 mmol) and chloroacetylchloride (549 μL, 6.9 mmol) to consume all the starting amine with continued stirring for 2 h. Pour into a separatory funnel containing 1 N HCl (200 mL) and extract with CH2Cl2 (2×250 mL). Wash the combined organic extracts with brine (200 mL), dry over Na2SO4, and concentrate to give crude N—((S)-1-benzyloxymethyl-2-hydroxy-ethyl)-2-chloro-acetamide. Dissolve this intermediate in THF (75 mL), cool to 0° C., and treat with NaH (1.1 g, 27.6 mmol). Stir 6 h at 0° C. to form the NH morpholinone. Add additional NaH 1.1 g (27.6 mmol) followed by MeI (3.6 mL, 57.5 mmol). Stir at 0° C. for 30 min and then pour into a separatory funnel containing 0.1 M HCl (200 mL). Extract with EtOAc (2×250 mL). Wash the combined organic extracts with brine (200 mL), dry over Na2SO4, filter, and concentrate to give the crude methylated product. Purify via silica gel chromatography using a gradient of 0-100% EtOAc/hexanes to yield 1.3 g (24%, 3 steps) of the title compound. MS/ES m/z 236.1 [M+H]+.

1. dissolutiondissolves
2. stirringStir 1 h
3. customto consume all the starting amine
4. stirringwith continued stirring for 2 h
5. additionPour into a separatory funnel
6. additioncontaining 1 N HCl (200 mL)
7. extractionextract with CH2Cl2 (2×250 mL)
8. washWash the combined organic extracts with brine (200 mL)
9. dry with materialdry over Na2SO4
10. concentrationconcentrate

ORD record

ord-1013986331c5421986585c8e5799294c

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08263772B2