Preparation background and overview of 3-aminomethyl-morpholine-4-tert-butyl carbonate
3-Aminomethyl-morpholine-4-tert-butyl carbonate can be used as a pharmaceutical synthesis intermediate. If 3-aminomethyl-morpholine-4-tert-butyl carbonate is inhaled, move the patient to fresh air; if skin contact occurs, remove contaminated clothing and rinse the skin thoroughly with soap and water. If there is any discomfort If you feel sick, seek medical attention; if eye contact occurs, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.
Preparation of 3-aminomethyl-morpholine-4-tert-butyl carbonate
The preparation of 3-aminomethyl-morpholine-4-tert-butyl carbonate is divided into the following steps:
Step 1: N-(4-benzyl-morpholin-3-ylmethyl)-2,2,2-trifluoroacetamide
To a solution of (4-benzyl-morpholin-3-yl)-methanamine (7.34g) in dichloromethane (240ml) was added triethylamine (5.83ml) and incubated at 0°C for 25 minutes. Add trifluoroacetic anhydride (8.23g) dropwise. The reaction mixture was allowed to reach ambient temperature, stirred for 18 hours, diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate solution. The organic phase was separated, dried and evaporated to give a brown gum which was purified on silica gel eluting with an ethyl acetate-pentane mixture to give the title product (5.17g) as an orange gum. Mass spectrum (API+): measured value 303 (MH+). C14H17F3N2O2 requires 302.
Step 2: 2,2,2-trifluoro-N-morpholin-3-ylmethylacetamide
To the product of step 1) (1.62g) in methanol (40ml) was added boric acid, palladium black (0.45g) and formic acid (10 drops), and the mixture was stirred at ambient temperature for 16 hours. Additional palladium black (0.225g) and formic acid (10 drops) were added and after 1 hour the reaction mixture was filtered through Celite and the filtrate was evaporated to an orange gum. Re-evaporation from dichloromethane gave the title compound (1.4g) as a pink solid. Mass spectrum (API+): measured value 213 (MH+). C7H11F3N2O2 requires 212.
Step 3: 3-[(2,2,2-trifluoroethylamino)-methyl]lepidolite-morpholine-4-carboxylic acid tert-butyl ester
A mixture of the compound of step 2) (1.75g), triethylamine (2.25ml) and di-tert-butyl dicarbonate (3.59g) in dichloromethane (75ml) was stirred at ambient temperature for 18 hours. The reaction mixture was diluted with dichloromethane, washed successively with 2M hydrochloric acid, water and brine, dried and evaporated to a gum. Chromatography on silica gel, eluting with an ethyl acetate-pentane mixture, gave the title compound (1.70 g) as a pale yellow solid.
Step 4: 3-Aminomethyl-morpholine-4-carboxylic acid tert-butyl ester
A mixture of the compound from step 3) (1.7g) and potassium carbonate (3.77g) in methanol (80ml) and water (27ml) was stirred at ambient temperature for 4 hours and then heated at 50°C for a further 2 hours. . The reaction mixture was concentrated to remove methanol, diluted with water and extracted with ethyl acetate (x3) and dichloromethane (x4). The combined extracts were dried and evaporated to give the title product 3-aminomethyl-morpholine-4-tert-butyl carbonate (0.97 g) as a yellow gum. Mass spectrum (API+): measured value 116 (MH-tBoc)+.
