Methanol → HCID 13032694, compound

Temperature

20 °C

A catalyst solution was prepared in a glove box (O2 content<1 ppm) by dissolving 385 mg (0.5 mmol) of [Ru(OAc)2((R)-BIPHEMP)] in 40 ml of a 0.025 molar methanolic hydrochloric acid solution and 40 ml of methylene chloride, subsequently stirred at 20° C. for 1.5 hours and thereafter transferred into a pressure-tight catalyst supply vessel. A 2 l steel autoclave was charged with 71.6 g (0.5 mol) of 2-keto-3,3,N-trimethyl-butyramide and 310 ml of methanol and sealed. After replacement of the atmosphere with hydrogen the catalyst solution was allowed to flow from the catalyst supply vessel into the autoclave with slight over-pressure and the hydrogenation was carried out while stirring at 60° C. and at a pressure of 60 bar (6 MPa). After 20 hours the hydrogenation was interrupted and the reaction mixture was evaporated. From a solution of the residue in 250 ml of diisopropyl ether there firstly separated at room temperature 1.2 g of crystalline product with ee=3% and a melting point of 135-137° C. By adding 275 ml of cyclohexane and stirring the mixture in an ice bath for 3 hours there were isolated 43.9 g (60.5%) of (R)-2-hydroxy-3,3,N-trimethyl-butyramide; m.p. 69-71° C.; [α]=+61.0° (c=1, CHCl3), ee=98.7% (measured by GC on an OV-61/p-DiMe-β-CD chiral column).

1. customsealed
2. stirringwhile stirring at 60° C. and at a pressure of 60 bar (6 MPa)
3. waitAfter 20 hours the hydrogenation was interrupted
4. customthe reaction mixture was evaporated
5. customFrom a solution of the residue in 250 ml of diisopropyl ether there firstly separated at room temperature 1.2 g of crystalline product with ee=3%
6. additionBy adding 275 ml of cyclohexane
7. stirringstirring the mixture in an ice bath for 3 hours there

ORD record

ord-3753ac610ded420d951950cc16d34518

Source dataset

uspto-grants-2002_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06348612B1