Lithium Hydroxide → HCID 58256674, compound

HRID 241948Notes

Reaction equation

HRID 241948 reaction equation
CO[C:3]([C:5]1[N:6]=[CH:7][NH:8][CH:9]=1)=[O:4].C(N(CC)CC)C.Cl[C:18]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[OH-].[Li+].[Cl:39]CCl>O.C1COCC1.CC(N(C)C)=O.C(O)(=O)C>[C:18]([N:8]1[CH:9]=[C:5]([C:3]([Cl:39])=[O:4])[N:6]=[CH:7]1)([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

10

Reactant 5

HCID 3939Lithium HydroxideHCID 6344DichloromethaneHCID 6456Trityl chlorideHCID 8471TriethylamineHCID 178418785HCID 178418785, compound

Product 1

HCID 58256674HCID 58256674, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

Methyl-4-imidazolecarboxylate (9.20 g, 73.0 mmol) is taken up in 130 mL dichloromethane and triethylamine (20.2 mL, 146 mmol) and chlorotriphenylmethane (22.4 g, 80.2 mmol) are added. The reaction mixture is stirred overnight at RT. The reaction mixture is washed with an aqueous 5% NaHCO3 solution and the organic phase is dried over MgSO4 and concentrated under reduced pressure. Yield: 26.9 g, mixture of regeo-isomers. The isomeric product is taken up in 80 mL methanol, a solution of lithium hydroxide (3.50 g, 24.0 mmol) in 100 mL water is added drop-wise and the reaction mixture is stirred overnight at RT. The reaction mixture is acidified to pH4 with acetic acid and extracted once with 200 mL and once with 100 mL dichloromethane. The organic phases are combined, dried over MgSO4 and concentrated under reduced pressure. The residue is triturated with 100 mL cyclohexane containing 10% ethyl acetate. Yield: 10.5 g, mixture of regeoisomers. The isomeric product (3.00 g, 8.47 mmol) is taken up in 5 mL dry THF and 1-chloro-N,N-2-trimethylpropenylamine (2.15 mL, 16.1 mL) and 1 mL dimethylacetamide are added. The reaction mixture is stirred for 0.5 h at RT and concentrated under reduced pressure. Yield: 3.2 g.

Workup

  1. washThe reaction mixture is washed with an aqueous 5% NaHCO3 solution
  2. dry with materialthe organic phase is dried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. additionYield: 26.9 g, mixture of regeo-isomers
  5. stirringthe reaction mixture is stirred overnight at RT
  6. extractionextracted once with 200 mL and once with 100 mL dichloromethane
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is triturated with 100 mL cyclohexane containing 10% ethyl acetate
  10. additionYield: 10.5 g, mixture of regeoisomers
  11. stirringThe reaction mixture is stirred for 0.5 h at RT
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0a48109ea9f244ff9740136a65333804
Source dataset
uspto-grants-2014_02
Patent number
US08653097B2

Reaction notes

Loading…