Dimethylformamide → HCID 59685163, compound

HRID 899432Notes

Reaction equation

HRID 899432 reaction equation
[CH3:1][O:2][CH2:3]Cl.[Br:5][C:6]1[CH:7]=[C:8]([OH:17])[CH:9]=[C:10]2[C:15]=1[O:14][C:13](=[O:16])[CH:12]=[CH:11]2.C([O-])([O-])=O.[K+].[K+].CN(C=O)C>CCOC(C)=O>[Br:5][C:6]1[CH:7]=[C:8]([O:17][CH2:1][O:2][CH3:3])[CH:9]=[C:10]2[C:15]=1[O:14][C:13](=[O:16])[CH:12]=[CH:11]2

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7864Chloromethyl Methyl Ether2×HCID 11430Potassium CarbonateHCID 59685165HCID 59685165, compound

Product 1

HCID 59685163HCID 59685163, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Add BBr3 (0.75 mL, 8 mmol) to preparation 3(662 mg, 2.0 mmol) in 20 mL of dichloromethane at 0° C. Let stir for 15 min. Add 8 mL of methanol and then concentrate. Adsorb to 6 g of silica gel and purify by flash chromatography (40 g, 10-50% A/B, A=10% MeOH in EtOAc, B=hexanes) to give 476 mg of 8-Bromo-6-hydroxy-chromen-2-one (3). Add chloromethyl methyl ether (0.18 mL) to a solution of 8-bromo-6-hydroxy-chromen-2-one (476 mg, 1.97 mmol) and K2CO3 (660 mg, 4.77 mmol) in 10 of DMF. Let the solution stir overnight, add 0.09 mL more chloromethyl methyl ether, let stir 2 hrs, dilute with EtOAc, wash with water, 1:1 water:brine, brine, dry (Na2SO4), filter and concentrate to yield 524 mg (1.84 mmol, 93%) of preparation 5. 1H NMR (400 MHz, CDCl3) δ 7.63 (d, 1H, J=9.2 Hz), 7.50 (d, 1H, J=2.6 Hz), 7.12 (d, 1H, J=2.6 Hz), 6.46 (d, 1H, J=9.7 Hz), 5.20 (s, 2H), 3.50 (s, 3H).

Workup

  1. stirringlet stir 2 hrs
  2. washwash with water, 1:1 water
  3. dry with materialbrine, brine, dry (Na2SO4)
  4. filtrationfilter
  5. concentrationconcentrate
  6. customto yield
  7. custom524 mg (1.84 mmol, 93%) of preparation 5

Sources & evidence

ORD record
ord-f2c79529cca14f75a26a8d8b8f05579b
Source dataset
uspto-grants-2008_04
Patent number
US07354951B2

Reaction notes

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