Hydrochloric Acid → HCID 58935008, compound

HRID 855127Notes

Reaction equation

HRID 855127 reaction equation
I[C:2]1[CH:3]=[C:4]([O:21][C:22]([F:25])([F:24])[F:23])[CH:5]=[C:6]2[C:11]=1[O:10][CH:9]([C:12]([F:15])([F:14])[F:13])[C:8]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:7]2.[CH3:26][CH2:27][O:28]CC.C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:60]([O-:63])([O-])=[O:61].[K+].[K+].Cl.[OH2:67]>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:26]([C:2]1[CH:3]=[C:4]([O:21][C:22]([F:24])([F:25])[F:23])[CH:5]=[C:6]2[C:11]=1[O:10][CH:9]([C:12]([F:14])([F:15])[F:13])[C:8]([C:60]([OH:63])=[O:61])=[CH:7]2)(=[O:67])[CH3:27].[C:27]([C:2]1[CH:3]=[C:4]([O:21][C:22]([F:23])([F:24])[F:25])[CH:5]=[C:6]2[C:11]=1[O:10][CH:9]([C:12]([F:14])([F:15])[F:13])[C:8]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:7]2)(=[O:28])[CH3:26]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 962WaterHCID 3283Diethyl EtherHCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 86599457ethyl 8-iodo-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Product 2

HCID 58935008HCID 58935008, compoundYield 29%HCID 86599502HCID 86599502, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 8-iodo-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate prepared as in Example 21a, Step 2 (9.64 g, 20.0 mmole), n-buytylvinyl ether (12.9 mL, 100 mmole), Pd(OAc)2 (135 mg, 0.600 mmole), DPPP (544 mg, 1.32 mmole) and K2CO3 (3.32 g, 24.0 mmole), in a mixture of DMF (50 mL) and H2O (6 mL) was stirred at 100° C. for 46 hrs. After the mixture was cooled to room temperature, 1N HCl (100 mL) was then added and the mixture was extracted with EtOAc (2×200 mL). The extracts were combined and washed with H2O (200 mL), brine (100 mL), dried over MgSO4 and filtered. The solvent was removed in vacuo and the crude product was purified by silica chromatography (20% EtOAc in hexanes with 1% HOAc) to give 2.12 g (29% yield) of 8-acetyl-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid prepared as in Example 21b as well as 1.44 g (18% yield) of the title compound as a yellow crystalline solid: ESHRMS m/z 399.0654 (M+H, C16H13F6O5, Calc'd 399.0662).

Workup

  1. temperatureAfter the mixture was cooled to room temperature
  2. extractionthe mixture was extracted with EtOAc (2×200 mL)
  3. washwashed with H2O (200 mL), brine (100 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customThe solvent was removed in vacuo
  7. customthe crude product was purified by silica chromatography (20% EtOAc in hexanes with 1% HOAc)
  8. customto give

Sources & evidence

ORD record
ord-26ee6c0da7aa4ff4898a916121948396
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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