HCID 58636705, compound → HCID 58636730, compound

HRID 1158972Notes

Reaction equation

HRID 1158972 reaction equation
[C:1]([O:5][C:6](=[O:36])[N:7]([CH2:16][C:17]1[CH:18]=[N:19][C:20]([CH3:35])=[C:21]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]#[N:34])[CH:28]=2)[C:22]=1[CH:23]=[O:24])[C:8]1[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:37][Mg]Br>O1CCCC1>[C:1]([O:5][C:6](=[O:36])[N:7]([CH2:16][C:17]1[CH:18]=[N:19][C:20]([CH3:35])=[C:21]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]#[N:34])[CH:28]=2)[C:22]=1[CH:23]([OH:24])[CH3:37])[C:8]1[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 58636705HCID 58636705, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 58636730HCID 58636730, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(3-cyano-benzyloxy)-4-formyl-6-methyl-pyridin-3-ylmethyl]-(4-cyano-phenyl)-carbamic acid tert-butyl ester (109) (1.4 g, 2.9 mmol) in anhydrous tetrahydrofuran (50 mL) was slowly added methyl magnesium bromide (4 mL, 1.0 M, 4.0 mmol) at −78° C. under nitrogen atmosphere and stirred for 30 minutes. The reaction mixture was quenched with a solution of saturated aqueous sodium bicarbonate, and the crude product extracted with ethyl acetate and dried over anhydrous magnesium sulfate. Evaporation of the solvent gave a crude residue, which was purified by column chromatography on silica gel using a gradient mixture of ethyl acetate:hexane (0:1 to 3:2) as an eluant to give [5-(3-cyano-benzyloxy)-4-(1-hydroxy-ethyl)-6-methyl-pyridin-3-ylmethyl]-(4-cyano-phenyl)-carbamic acid tert-butyl ester (112) (1.04 g, 72% yield).

Workup

  1. customat −78° C.
  2. customThe reaction mixture was quenched with a solution of saturated aqueous sodium bicarbonate
  3. extractionthe crude product extracted with ethyl acetate
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customEvaporation of the solvent
  6. customgave a crude residue, which
  7. customwas purified by column chromatography on silica gel using
  8. additiona gradient mixture of ethyl acetate:hexane (0:1 to 3:2) as an eluant

Sources & evidence

ORD record
ord-27de7c01e3c643d4922e4568b64c71c0
Source dataset
uspto-grants-2010_10
Patent number
US07812037B2

Reaction notes

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