Triethylamine → 5-(t-Butoxyacetamido)-6-bromoindan-1-one

Participants

Reaction Conditions

Reaction Steps

A flame-dried 10 L, 4 necked round bottom flask was equipped with a mechanical stirrer, a reflux condenser, a thermo-socket and a nitrogen inlet. The flask was charged with tert-butoxyacetic acid (250 g, 1.89 mol, 1 eq) and dry dichloromethane (6.25 L). The flask was cooled in an ice-salt mixture to −5-0° C. To the solution was added diethyl chlorophosphate slowly over a period of 15 min (816 g, 4.72 mol, 2.5 eq) followed by the dropwise addition of triethylamine (478 g, 4.73 mol, 2.5 eq) over a period of 30 minutes with the temperature of the reaction not exceeding 25° C. during the addition. The stirred reaction mixture was gradually allowed to warm to 25-30° C. for one hour and then 5-amino-6-bromo-1-indanone (282.5 g, 1.25 mol, 0.66 eq) and triethylamine (478 g, 4.73 mol, 2.5 eq) were added. The reaction was refluxed for 24 hours and an aliquot was removed and analyzed by HPLC. The reaction was found to be complete (Starting material <0.5%). The solvent was removed on the rotary evaporator in vacuo affording a brown viscous residue. To the residue was added 4.7 L of a 20% methanol/water mixture. The sticky mixture was stirred with a mechanical stirrer for 20 hours. A free flowing solid formed which was filtered off and washed with 500 ml of water and dried at 55° C. in vacuo for 8 hours. 378 g (89%) of the desired tert-butoxyacetanilide was obtained as a tan powder after drying.

Provenance & Evidence