反应详情

A solution of 0.09 g (0.276 mmol) of trans-4-{[(4-chloro-phenoxycarbonyl)-methyl-amino]-methyl}-cyclohexanecarboxylic acid in 2.5 mL of CH2Cl2 was treated at RT with 1 drop of DMF. 0.026 mL (0.304 mmol, 1.1 eq) of oxalyl chloride was added within 5 min and stirring was continued for 90 min. The solution was evaporated, redissolved in 2.5 mL of CH2Cl2 and added to a solution of 0.197 mL (2.21 mmol, 7.2 eq) of 3-(methylamino)-1-propanol [Powell et al., Synthesis (1986), (4), 338-40]at 0° C. The reaction was kept over night at RT, then partitioned between Et2O (×3)/aqueous saturated NaHCO3. The organic phases were washed once with aqueous 10% NaCl, dried over Na2SO4 and evaporated. Purification by flash-chromatography on 5 g silica gel (EtOAc:CH2Cl2 1:9 to 9:1) gave 0.064 g (58%) of pure trans-{4-[(3-hydroxy-propyl)-methyl-carbamoyl]-cyclohexylmethyl}-methyl-carbamic acid 4-chloro-phenyl ester, MS: 397 (MH+, 1Cl).

1. customThe solution was evaporated
2. dissolutionredissolved in 2.5 mL of CH2Cl2
3. customPowell et al., Synthesis (1986), (4), 338-40]at 0° C
4. waitThe reaction was kept over night at RT
5. custompartitioned between Et2O (×3)/aqueous saturated NaHCO3
6. washThe organic phases were washed once with aqueous 10% NaCl
7. dry with materialdried over Na2SO4
8. customevaporated
9. customPurification by flash-chromatography on 5 g silica gel (EtOAc:CH2Cl2 1:9 to 9:1)