Tert-butyl 3-hydroxyazetidine-1-carboxylate → Tert-butyl 3-((3-(3,6-dihydro-2H-pyran-4-YL)pyridin-2-YL)oxy)azetidine-1-carboxylate

HRID 454906Notes

Reaction equation

HRID 454906 reaction equation
Cl[C:2]1[C:7]([C:8]2[CH2:9][CH2:10][O:11][CH2:12][CH:13]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[OH:14][CH:15]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]1.CC(C)([O-])C.[Na+]>CS(C)=O.O>[O:11]1[CH2:12][CH:13]=[C:8]([C:7]2[C:2]([O:14][CH:15]3[CH2:16][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18]3)=[N:3][CH:4]=[CH:5][CH:6]=2)[CH2:9][CH2:10]1

Participants

6

Reactant 3

HCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylateHCID 23676156Sodium t-butoxideHCID 585477502-chloro-3-(3,6-dihydro-2H-pyran-4-yl)pyridine

Product 1

HCID 58547888Tert-butyl 3-((3-(3,6-dihydro-2H-pyran-4-YL)pyridin-2-YL)oxy)azetidine-1-carboxylateYield 75%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

2-chloro-3-(3,6-dihydro-2H-pyran-4-yl)-pyridine (see PREPARATION P13.1; 3.5 g, 17.9 mmol) and tert-butyl 3-hydroxyazetidine-1-carboxylate (2.8 g, 17.9 mmol) were dissolved in DMSO (20 mL) and sodium tert-butoxide (t-BuONa) (3.4 g, 35.8 mmol) was added to the above solution. The reaction mixture was stirred at room temperature for overnight. The reaction mixture was diluted with water and extracted with ethyl acetate (2×10 mL). The combined organic layers were dried over Na2SO4 and concentrated to give the crude product. The crud product was purified by silica gel column chromatography to give the title compound (2.3 g, 7.8 mmol, yield 75%). 1H NMR (DMSO-D6, 300 MHz) δ (ppm) 1.38 (s, 9H), 2.41-2.47 (m, 2H), 3.75-3.86 (m, 4H), 4.19-4.30 (m, 4H), 5.26-5.35 (m, 1H), 6.15-6.20 (m, 1H), 7.01 (dd, 1H, J=7.31 Hz, 4.97 Hz), 7.62 (d, 1H, J=7.45 Hz), 8.02 (d, 1H, J=4.82 Hz)

Workup

  1. extractionextracted with ethyl acetate (2×10 mL)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated
  4. customto give the crude product
  5. customThe crud product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-32e68e3e03b5401e8290c8a8b5a2c5b7
Source dataset
uspto-grants-2013_07
Patent number
US08497265B2

Reaction notes

Loading…