Tributyl[(methoxymethoxy)methyl]stannane → 1-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazol-5-yl]-2-methoxymethoxy-ethanol

HRID 1676463Notes

Reaction equation

HRID 1676463 reaction equation
C([Sn](CCCC)(CCCC)[CH2:6][O:7][CH2:8][O:9][CH3:10])CCC.[Li]CCCC.[Br:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]2[C:33]([CH:43]=[O:44])=[CH:34][C:35]3[N:39]([CH3:40])[CH:38]=[N:37][C:36]=3[C:41]=2[F:42])=[C:27]([Cl:45])[CH:26]=1>C1COCC1>[Br:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]2[C:33]([CH:43]([OH:44])[CH2:6][O:7][CH2:8][O:9][CH3:10])=[CH:34][C:35]3[N:39]([CH3:40])[CH:38]=[N:37][C:36]=3[C:41]=2[F:42])=[C:27]([Cl:45])[CH:26]=1

Participants

5

Reactant 3

HCID 4193592Tributyl[(methoxymethoxy)methyl]stannaneHCID 211142076-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 211141711-[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazol-5-yl]-2-methoxymethoxy-ethanolYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tributyl-methoxymethoxymethyl-stannane (864 mg, 2.37 mmol, prepared by the procedure reported in J. Org. Chem. 1988, 53, 4131) in THF (8 mL) at −78° C. is added n-BuLi (0.94 mL, 2.35 mmol, 2.5 M solution in hexane). After stirring for 3 minutes, a solution of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carbaldehyde 10 h (59 mg, 0.15 mmol) in THF (2 mL) is added at −78° C. After stirring for 40 minutes at −78° C., the reaction is quenched with saturated aqueous NH4Cl at −78° C., warmed to room temperature, and diluted with EtOAc. The organic layer is washed with brine, dried over MgSO4, filtered, concentrated, and purified by flash chromatography (1.5% MeOH in CH2Cl2) to give the desired product (45 mg, 64%): MS APCI (+) m/z 458, 460 (M+, Br pattern) detected.

Workup

  1. stirringAfter stirring for 40 minutes at −78° C.
  2. customthe reaction is quenched with saturated aqueous NH4Cl at −78° C.
  3. additiondiluted with EtOAc
  4. washThe organic layer is washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by flash chromatography (1.5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-b7c50a40a1a24afe91b008533a6b6394
Source dataset
uspto-grants-2011_08
Patent number
US08003805B2

Reaction notes

Loading…