Sodium hydride → 4-(Furo[3,2-c]pyridin-2-ylmethoxy)piperidine-1-carboxylic acid tert-butyl ester

HRID 217180Notes

Reaction equation

HRID 217180 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl.Br[CH2:19][C:20]1[O:28][C:27]2[CH:26]=[CH:25][N:24]=[CH:23][C:22]=2[CH:21]=1>C1COCC1.[N+](CCCC)(CCCC)(CCCC)CCCC.[I-]>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][CH2:19][C:20]2[O:28][C:27]3[CH:26]=[CH:25][N:24]=[CH:23][C:22]=3[CH:21]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 3

HCID 24758Sodium hydride2×HCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 68939591Furo[3,2-c]pyridine,2-(bromomethyl)-,hydrochloride

Product 1

HCID 576595644-(Furo[3,2-c]pyridin-2-ylmethoxy)piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
20 °C

Procedure

NaH (4.4 mg of a 60% dispersion in mineral oil, 110 μmol) was added to a stirred solution of 4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (20.2 mg, 100 μmol) in anhydrous THF (1 mL). After 1 h, the mixture was added to a stirred solution of 2-bromomethylfuro[3,2-c]pyridine hydrochloride (Preparation 5, 25.0 mg, 100 μmol) in anhydrous THF (2 mL) which had been pretreated with NaH (4.4 mg of a 60% dispersion in mineral oil, 110 μmol). The mixture was stirred for 16 h at 20° C., before being treated with Bu4NI (3.7 mg, 10 μmol) and heated at 60° C. for 4 h. On cooling, the reaction mixture was quenched with H2O (5 mL), before being extracted with EtOAc (2×5 mL). The combined organic extracts were dried (MgSO4), filtered, concentrated, and purified by flash chromatography (IH-EtOAc, 2:3) to yield the title compound: RT=2.64 min; m/z (ES+)=333.3 [M+H]+.

Workup

  1. temperatureheated at 60° C. for 4 h
  2. temperatureOn cooling
  3. customthe reaction mixture was quenched with H2O (5 mL)
  4. extractionbefore being extracted with EtOAc (2×5 mL)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by flash chromatography (IH-EtOAc, 2:3)

Sources & evidence

ORD record
ord-7e5d8aa72cfd4846a0a4217a88ff3734
Source dataset
uspto-grants-2012_06
Patent number
US08193359B2

Reaction notes

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