tert-Butanol → 2-({2-[2-(1-Methylpyrrolidin-2-yl)ethoxy]pyridin-3-yl}oxy)ethanol

HRID 1765072Notes

Reaction equation

Cl[C:2]1[C:7]([O:8][CH2:9][CH2:10][O:11]C2CCCCO2)=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:18][N:19]1[CH2:23][CH2:22][CH2:21][CH:20]1[CH2:24][CH2:25][OH:26].CC(C)([O-])C.[K+].C(O)(C)(C)C>C1(C)C=CC=CC=1>[CH3:18][N:19]1[CH2:23][CH2:22][CH2:21][CH:20]1[CH2:24][CH2:25][O:26][C:2]1[C:7]([O:8][CH2:9][CH2:10][OH:11])=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 2-chloro-3-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridine (from Example 4; 100 mg, 0.39 mmol), 1-methyl-2-pyrrolidineethanol (79 μl, 0.58 mmol) and 1.0 M potassium tert-butoxide in tert-butanol (0.8 mL, 0.80 mmol) in 4 mL of toluene was heated at 100° C. for 1 day. The organic phase was washed with 3×2 mL of water and 2 mL of brine. The organic phase was shaken at 50° C. with 4 mL of 2.0 M acetic acid for 2 days. The aqueous phase was washed with 3×3 mL of ethyl acetate, made basic by addition of potassium hydroxide, saturated with sodium chloride and extracted with 3×2 mL of ethyl acetate. The organic phase was dried (MgSO4) and concentrated under reduced pressure to give 55 mg (0.21 mmol, 53%) of the title compound as a colorless oil. LC-UV purity 95%. MS m/z 267 (M+1)+, calc. 267 (M+1)+.

Workup

washThe organic phase was washed with 3×2 mL of water and 2 mL of brine
washThe aqueous phase was washed with 3×3 mL of ethyl acetate
additionmade basic by addition of potassium hydroxide, saturated with sodium chloride
extractionextracted with 3×2 mL of ethyl acetate
dry with materialThe organic phase was dried (MgSO4)
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-9ee7aed36de84494b83947fdc9b8bc95
Source dataset: uspto-grants-2007_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07226925B2

Reaction notes

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