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

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.

1. temperaturecooled in an ice water bath
2. concentrationthe reaction mixture was concentrated in vacuo
3. additionDMF (100 mL) was added
4. customthis was also removed in vacuo (
5. customto remove any unreacted trimethylacetyl chloride, bp 105-106° C.)
6. dissolutionThe crude product was redissolved in CH2Cl2 (150 mL)
7. waitAfter 1 h
8. concentrationthe reaction mixture was concentrated in vacuo
9. custompartitioned between EtOAc and water
10. customAfter separation of the layers
11. washthe EtOAc solution was washed with dilute NaHCO3 and water
12. concentrationThe EtOAc solution was concentrated in vacuo
13. customto give the crude product
14. customThis material was purified by chromatography (97:3 EtOAc/MeOH)

ORD-Eintrag

ord-c08976ab8a004d869a914b1c426b46d5

Quelldatensatz

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07998462B2