Sodium hydride → tert-butyl 3-chloro-7-(tetrahydrofuran-3-yl)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate

HRID 1777837Notes

Reaction equation

HRID 1777837 reaction equation
[C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]([C:14]1[C:19]([CH2:20]Cl)=[CH:18][C:17]([Cl:22])=[CH:16][N:15]=1)[CH:9]1[CH2:13][CH2:12][O:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:7]1[CH2:20][C:19]2[C:14](=[N:15][CH:16]=[C:17]([Cl:22])[CH:18]=2)[CH:8]1[CH:9]1[CH2:13][CH2:12][O:11][CH2:10]1)=[O:23])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 131734771Tert-butyl((5-chloro-3-(chloromethyl)pyridin-2-yl)(tetrahydrofuran-3-yl)methyl)carbamate

Product 1

HCID 118274928tert-butyl 3-chloro-7-(tetrahydrofuran-3-yl)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylateYield 92.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl((5-chloro-3-(chloromethyl)pyridin-2-yl)(tetrahydrofuran-3-yl)methyl)carbamate (470 mg, 0.95 mmol) in anhydrous DMF (5 mL) was added with sodium hydride (115 mg, 2.84 mmol, 60% in mineral oil) in portions at 0° C. The mixture was stirred at rt for 2 h. The mixture was quenched with water (40 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure and purified by chromatography column on silica gel (eluting with 10% EtOAc in petroleum ether) to afford tert-butyl3-chloro-7-(tetrahydrofuran-3-yl)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate (285 mg, 91%) as a colorless oil. LCMS: tR=0.862 min in 5-95AB—1.5 min chromatography (MK RP-18e 25-2 mm), MS (ESI) m/z 324.9 [M+H]+. 1H NMR (CD3OD, 400 MHz): δ 8.47 (s, 1H), 7.83 (d, J=13.6 Hz, 1H), 5.10 (s, 1H), 4.65-4.50 (m, 1.5H), 3.95 (t, J=8.0 Hz, 0.5H), 3.85-3.67 (m, 4H), 3.03-2.87 (m, 1H), 2.15-1.65 (m, 2H), 1.54 (s, 9H).

Workup

  1. customThe mixture was quenched with water (40 mL)
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. custompurified by chromatography column on silica gel (eluting with 10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-fe45ed8fcff3459887cac146a8f3109c
Source dataset
uspto-grants-2016_02
Patent number
US09266886B2

Reaction notes

Loading…