1,2-Dimethoxyethane → Methyl 4-[2-(hydroxymethyl)-1-benzofuran-5-yl]Benzoate

HRID 1836954Notes

Reaction equation

HRID 1836954 reaction equation
COCCOC.Br[C:8]1[CH:9]=[CH:10][C:11]2[O:15][C:14]([CH2:16][OH:17])=[CH:13][C:12]=2[CH:18]=1.[CH3:19][O:20][C:21]([C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1)=[O:22].C([O-])([O-])=O.[Na+].[Na+]>CO.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CO.C(Cl)Cl>[OH:17][CH2:16][C:14]1[O:15][C:11]2[CH:10]=[CH:9][C:8]([C:26]3[CH:27]=[CH:28][C:23]([C:21]([O:20][CH3:19])=[O:22])=[CH:24][CH:25]=3)=[CH:18][C:12]=2[CH:13]=1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27343694-Methoxycarbonylphenylboronic acidHCID 2795537(5-Bromo-1-benzofuran-2-yl)methanol

Product 1

HCID 12144835Methyl 4-[2-(hydroxymethyl)-1-benzofuran-5-yl]BenzoateYield 80%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 887MethanolSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To 4 mL DME under Ar was added (5-bromo-1-benzofuran-2-yl)methanol (Example 3, 250 mg, 1.10 mmol) and Ar was bubbled through the mixture for 2 minutes to remove any dissolved oxygen. To this mixture was then added 37.6 mg (0.033 mmol) tetrakis(triphenylphosphine) palladium(0) and the reaction was stirred for 10 minutes at rt. 4-(Methoxycarbonyl)phenyl boronic acid (218 mg, 1.21 mmol) and 2.64 mL of 1 M Na2CO3 were then added, and the mixture was then heated to 100° C. for 2.5 hours under Ar. At the end of this time, TLC (5% MeOH/CH2Cl2) revealed complete reaction. The mixture was then filtered and the DME removed under reduced pressure. The thick paste was then transferred to a separatory funnel with 80 mL water and 100 mL EtOAc. The EtOAc was separated and the aqueous phase extracted with EtOAc (2×100 mL). The combined organic layers were dried over Na2SO4, filtered, and solvent removed in vacuo to provide a dark brown solid. The solid was dissolved in a minimal amount of MeOH, fused to silica gel, and purified by flash chromatography (2.5% MeOH/CH2Cl2). The desired product (247.7 mg, 80%) was obtained as a white solid. 1H-NMR (acetone-d6, δ: 3.91 (s, 3H), 4.71 (s, 2H), 6.82 (s, 1H), 7.62 (m, 2H), 7.83 (d, 2H), 7.94 (m, 1H), 8.09 (d, 2H); LRMS (GC/MS/EI) 282 [M]+.

Workup

  1. customwas bubbled through the mixture for 2 minutes
  2. customto remove any dissolved oxygen
  3. temperaturethe mixture was then heated to 100° C. for 2.5 hours under Ar
  4. customreaction
  5. filtrationThe mixture was then filtered
  6. customthe DME removed under reduced pressure
  7. customThe thick paste was then transferred to a separatory funnel with 80 mL water and 100 mL EtOAc
  8. customThe EtOAc was separated
  9. extractionthe aqueous phase extracted with EtOAc (2×100 mL)
  10. dry with materialThe combined organic layers were dried over Na2SO4
  11. filtrationfiltered
  12. customsolvent removed in vacuo
  13. customto provide a dark brown solid
  14. custompurified by flash chromatography (2.5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-560a5a710f2c400db869687a1e674c23
Source dataset
uspto-grants-2004_08
Patent number
US06780859B2

Reaction notes

Loading…