Ammonium Chloride → ethyl 7-(3,4-difluorobenzyl)-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 854883Notes

Reaction equation

HRID 854883 reaction equation
I[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:8]([C:12]([F:15])([F:14])[F:13])[O:9]2)=[CH:4][CH:3]=1.[Br-].[F:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][C:30]=1[F:31])[CH2:26][Zn+].[NH4+].[Cl-]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[F:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][C:30]=1[F:31])[CH2:26][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:8]([C:12]([F:15])([F:14])[F:13])[O:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 69517680ethyl 7-iodo-2-(trifluoromethyl)-2H-chromene-3-carboxylateHCID 178505766HCID 178505766, compound

Product 1

HCID 69516645ethyl 7-(3,4-difluorobenzyl)-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of Pd(dba)2 (57.5 mg, 0.100 mmole) and tfp (46.7 mg, 0.201 mmole) in anhydrous THF (10.0 mL) was stirred at room temperature for 20 minutes and then cooled to 0° C. Ethyl 7-iodo-2-(trifluoromethyl)-2H-chromene-3-carboxylate prepared as in Example 9a, Step 2 (2.00 g, 5.02 mmole) was added as a solid, followed by a solution of 3,4-difluorobenzyl zinc bromide in anhydrous THF (20.0 mL-0.5 M, 0.100 mmole) added dropwise over 5 minutes. The mixture was stirred at 0° C. for 0.5 h, then at room temperature for 24 h and was then poured into sat. NH4Cl (100 mL) and extracted with EtOAc (2×200 mL). The combined extracts were washed with brine (50 mL), dried over MgSO4, filtered and concentrated in vacuo to give 3.45 g of an orange oil. The crude product was purified by silica chromatography (92.5:7.5 hexanes:EtOAc) to give 1.81 g (91 % yield) of the product as a yellow oil: EIHRMS m/z 398.0955 (M+, C20H15F5O3, Calc'd 398.0941).

Workup

  1. additionwas added as a solid
  2. additionadded dropwise over 5 minutes
  3. waitat room temperature for 24 h
  4. extractionextracted with EtOAc (2×200 mL)
  5. washThe combined extracts were washed with brine (50 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3c4726f7667c4ca087b3470873ba0616
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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