4-Methylmorpholine → DPC-AG1166-00 (L-Isomer)

Participants

Reaction Steps

To a solution of the crude phenoxybutanoic acid (20) from the previous reaction (2.75 g) in CH2Cl2 (150 mL) cooled in an ice water bath was added 4-methylmorpholine (0.89 g, 8.8 mmol) and then trimethylacetyl chloride (1.06 g, 8.8 mmol). The reaction mixture was allowed to warm to rt. After 1 h, the reaction mixture was concentrated in vacuo then DMF (100 mL) was added and this was also removed in vacuo (to remove any unreacted trimethylacetyl chloride, bp 105-106° C.). The crude product was redissolved in CH2Cl2 (150 mL) and a solution of benzyl N-(2-aminoethyl)carbamate hydrochloride, 21 (1.52 g, 6.6 mmol) and 4-methylmorpholine (1.11 g, 11.0 mmol) in DMF was added. After 1 h, the reaction mixture was concentrated in vacuo and partitioned between EtOAc and water. After separation of the layers, the EtOAc solution was washed with dilute NaHCO3 and water. The EtOAc solution was concentrated in vacuo to give the crude product. This material was purified by chromatography (97:3 EtOAc/MeOH) to give 2.80 g of product 22.

Provenance & Evidence