Ethyl Glycolate → HCID 117667113, compound

Hydroxy-acetic acid ethyl ester (3.7 g, 36 mmol) is added to a suspension of 60% NaH (1.5 g, 37 mmol) in DMF (70 ml) at 0° C. and the mixture is stirred at room temperature for 15 min. Then 3-bromo-5-chloromethyl-pyridine (3.0 g, 15 mmol) is added to the mixture at 0° C. and the mixture is stirred at room temperature for 16 hrs. The reaction is quenched with saturated. NH4Cl aqueous solution, extracted with EtOAc three times. The organic layers are combined, washed with water and brine, dried over Na2SO4 and concentrated. The residue is purified by flash column chromatography to give 1.6 g of (5-bromo-pyridin-3-ylmethoxy)-acetic acid ethyl ester. 1.0 M MeMgBr (7.5 mL, 7.5 mmol) is added dropwise to a solution of (5-bromo-pyridin-3-ylmethoxy)-acetic acid ethyl ester (1.6 g, 5.9 mmol) in THF (54 mL) at 0° C. The mixture is stirred at room temperature for 16 hrs. Then the mixture is diluted with EtOAc and washed with water and brine. The organic layer is separated, dried over Na2SO4 and concentrated. The residue is purified by flash column chromatography to give 600 mg of 1-(5-bromo-pyridin-3-ylmethoxy)-2-methyl-propan-2-ol. It is then converted to 6-[5-(2-hydroxy-2-methyl-propoxymethyl)-pyridin-3-yl]-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester according to the procedure of Suzuki Coupling Method IV.

1. stirringthe mixture is stirred at room temperature for 16 hrs
2. customThe reaction is quenched with saturated
3. extractionNH4Cl aqueous solution, extracted with EtOAc three times
4. washwashed with water and brine
5. dry with materialdried over Na2SO4
6. concentrationconcentrated
7. customThe residue is purified by flash column chromatography

ORD record

ord-e11cd2b5b1ca4897a35d9f14755c5203

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181272B2