Cesium carbonate → HCID 66977505, compound

HRID 1041913Notes

Reaction equation

HRID 1041913 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([CH3:13])[CH3:12])=[N:9][N:10]=2)[CH:7]=1.[OH:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22]([O:24]C(C)(C)C)=O)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C[N:36]1CCCC1=O>C(OCC)C.[Cu]Cl>[CH:11]([C:8]1[N:6]2[CH:7]=[C:2]([O:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([NH2:36])=[O:24])=[CH:17][CH:16]=3)[CH:3]=[CH:4][C:5]2=[N:10][N:9]=1)([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 13387N-methyl-2-pyrrolidoneHCID 15932404Tert-butyl 2-(4-hydroxyphenyl)acetateHCID 66977454HCID 66977454, compound

Product 1

HCID 66977505HCID 66977505, compoundYield 8%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 3283Diethyl EtherSolvent

Procedure

A solution of Example 23 step a (430 mg, 1.5 mmol), tert-butyl 2-(4-hydroxyphenyl)acetate (WO2008/024746, 621 mg, 3 mmol), cesium carbonate (978 mg, 3 mmol), copper (I) chloride (74 mg, 0.75 mmol) and 2,2,6,6-tetramethylheptanedione (28 mg, 0.15 mmol) in N-methylpyrrolidinone (2 mL) was heated at 115° C. for 1 h. The reaction mixture was left to cool to RT, diluted with diethyl ether and washed with water. The aqueous layer was extracted with EtOAc and DCM and the combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The resulting oil was purified on a SCX-2 cartridge eluting with EtOAc, MeOH then 1N ammonia in MeOH. The ammonia fractions were concentrated in vacuo and purified twice by FCC (DCM/MeOH containing NH3 10/0 to 9/1 then EtOAc) to provide the title compound as an orange gum (44 mg, 8%). LCMS (Method 8): Rt 4.30 min, m/z 368 [MH+].

Workup

  1. waitThe reaction mixture was left
  2. washwashed with water
  3. extractionThe aqueous layer was extracted with EtOAc and DCM
  4. dry with materialthe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting oil was purified on a SCX-2 cartridge
  8. washeluting with EtOAc, MeOH
  9. concentrationThe ammonia fractions were concentrated in vacuo
  10. custompurified twice by FCC (DCM/MeOH
  11. additioncontaining NH3 10/0 to 9/1

Sources & evidence

ORD record
ord-b6c81453a5d94c199a0e52fa95598150
Source dataset
uspto-grants-2013_10
Patent number
US08557797B2

Reaction notes

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