Acetonitrile → 6-Iodo-7-methoxy-3,4,4a,9a-tetrahydro-1H-benzo[4,5]furo[2,3-c]pyridine-2-carboxylic acid tert-butyl ester

HRID 1616918Notes

Reaction equation

HRID 1616918 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]2[C:14]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:15]=3[O:16][CH:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[I:23]Cl.C(#N)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>CO.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]2[C:14]3[CH:20]=[C:19]([I:23])[C:18]([O:21][CH3:22])=[CH:17][C:15]=3[O:16][CH:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 24640Iodine chlorideHCID 90495Di-tert-butyl dicarbonateHCID 67324335tert-butyl 7-methoxy-3,4,4a,9a-tetrahydro[1]benzofuro[2,3-c]pyridine-2(1H)-carboxylate

Product 1

HCID 683046876-Iodo-7-methoxy-3,4,4a,9a-tetrahydro-1H-benzo[4,5]furo[2,3-c]pyridine-2-carboxylic acid tert-butyl esterYield 45%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolvent2×

Procedure

To a solution of 7-methoxy-3,4,4a,9a-tetrahydro-1H-benzo[4,5]furo[2,3-c]pyridine-2-carboxylic acid tert-butyl ester (500 mg, 2 mmol) in methanol (7 mL, 200 mmol) was added dropwise a solution of iodine monochloride (340 mg, 2.1 mmol) in 5 ml of methanol at RT. The mixture was stirred overnight at RT. After 18 h, the solvent was removed and the crude reaction mixture was treated with 50 mL of acetonitrile, di-tert-butyl dicarbonate (0.5 mL) and 10 mg of DMAP (10 mg). The mixture was stirred overnight at RT. After 18 h, solvent was removed and the crude product was purified by ISCO chromatography (Hexane:EtOAc 70:30) which was obtained as a syrup (321 mg, 45%). MS m/z 454 [M+H]+

Workup

  1. waitAfter 18 h
  2. customthe solvent was removed
  3. customthe crude reaction mixture
  4. stirringThe mixture was stirred overnight at RT
  5. waitAfter 18 h
  6. customsolvent was removed
  7. customthe crude product was purified by ISCO chromatography (Hexane:EtOAc 70:30) which

Sources & evidence

ORD record
ord-1a3f41e06f494962a7cde1da43d3eeb5
Source dataset
uspto-grants-2014_07
Patent number
US08765779B2

Reaction notes

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