Citric Acid → HCID 11521293, compound

Participants

Reaction Steps

N-Boc-2-(3-hydroxy)benzylmorpholine, trifluoromethylsulfonate ester intermediate (a) (62 mg, 0.16 mmol) was dissolved in tetrahydrofuran (3 mL) and NMP (0.3 mL) under an atmosphere of nitrogen, at room temperature then iron (III) ac ethyl acetateetate (3 mg, 7.3 umol) was added in one portion to give an orange solution. To the reaction mixture was added ethylmagnesium chloride (2.0M solution in tetrahydrofuran, 0.11 mL, 0.22 mmol) dropwise over 2 minutes and the reaction stirred at room temperature for 30 minutes. Then more iron (III) ac ethyl acetateetate (6 mg, 14.6 umol) was added in one portion followed by ethylmagnesium chloride (2.0M solution in tetrahydrofuran, 0.24 mL, 0.48 mmol) dropwise over 3 minutes. After 30 minutes citric acid (10% w/w aqueous solution, 10 mL) and ethyl acetate (10 mL) was added and the mixture stirred vigorously for 5 minutes and left to stand for 18 hrs. The layers were separated and the aqueous layer extracted with ethyl acetate (10 mL). Combined organic layers were washed with water (10 mL), then brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in dichloromethane (2.5 mL) and treated with TFA (1 mL) and stirred at room temperature for 3 hrs. The reaction was then poured through an SCX-2 column and washed with dichloromethane. The column was then washed with ammonia (2N, methanol) and the ammonia washes concentrated in vacuo. The residue was purified by preparative HPLC to yield the desired morpholine example 69 as an off-white solid (6 mg).

Provenance & Evidence