Reaction #53854

Reaction equation

KHSO4

iodomethane

trans-[4-(Methoxy-methyl-carbamoyl)-cyclohexyl]-carbamic acid tert-butyl ester

NaH

→

trans-[4-(Methoxy-methyl-carbamoyl)-cyclohexyl]-methyl-carbamic acid tert-butyl ester

Yield 84.0%

Solvents

water Et2O

DMF

Conditions

Workup

1. 1
   Temperaturewarmed up to RT over night
2. 2
   TemperatureThe reaction is cooled
3. 3
   WashThe organic phase was washed with aqueous 10% NaCl
4. 4
   Dryingdried over Na2SO4
5. 5
   Otherevaporated
6. 6
   Otherpurified by flash silica gel column (CH2Cl2/EtOAc 9:1 to 1:1)

Procedure

A solution of 24.18 g (82 mmol) of trans-[4-(Methoxy-methyl-carbamoyl)-cyclohexyl]-carbamic acid tert-butyl ester in 80 ml of DMF was treated at 0° C. with 5.37 g (123 mmol) of 55% NaH in small portions. The reaction was stirred for 1 h at 0° C., then treated slowly (20 min) with 40.9 ml (656 mmol) iodomethane and warmed up to RT over night. The reaction is cooled and neutralized with aqueous 10% KHSO4 and poured into water/Et2O (3×). The organic phase was washed with aqueous 10% NaCl, dried over Na2SO4 evaporated and purified by flash silica gel column (CH2Cl2/EtOAc 9:1 to 1:1) to yield 20.69 g (84%) of trans-[4-(Methoxy-methyl-carbamoyl)-cyclohexyl]-methyl-carbamic acid tert-butyl ester, MS: 301 (MH+).

Source