Methyl iodide → HCID 58817651, compound

HRID 1986952Notes

Reaction equation

HRID 1986952 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:18]3[CH:19]=[CH:20][C:21]([F:24])=[C:22]([OH:23])[C:17]=3[O:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:25]C(C)([O-])C.[K+].IC>CN1CCCC1=O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[C:18]3[CH:19]=[CH:20][C:21]([F:24])=[C:22]([O:23][CH3:25])[C:17]=3[O:16][N:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 23665647Potassium tert-butoxideHCID 58817704HCID 58817704, compound

Product 1

HCID 58817651HCID 58817651, compoundYield 90.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirred solution of 4-(6-fluoro-7-hydroxy-benzo[d]isoxazol-3-yl)-piperidine-1-carboxylic acid tert-butyl ester (1.28 g, 3.80 mmol) in N-methyl-2-pyrrolidone (33 mL) was added potassium tert-butoxide (2.09 g, 17.12 mmoles). To the resulting deep red solution was added iodomethane (1.20 mL, 19.02 mmoles). The resulting yellow solution was stirred at room temperature for 6 hours when the reaction was quenched with water (55 mL) and acidified with HClaq. The resulting mixture was extracted with Et2O (4×110 mL). The combined extracts were washed with brine (110 mL), dried (MgSO4), filtered and evaporated. The residue was separated via column chromatography (1:1; Et2O/Pet. ether) yielding 1.2 g of the methyl ether. The white, solid product was further purified via recrystallization from 1:1; Et2O/Pet. ether yielding 963 mg (72%) as a white, crystalline solid, mp 94-96° C. Analysis calculated for C18H23N2FO4: 61.70% C, 6.62% H, 7.99% N. Found: 61.75% C, 6.73% H, 7.94% N.

Workup

  1. customwas quenched with water (55 mL)
  2. extractionThe resulting mixture was extracted with Et2O (4×110 mL)
  3. washThe combined extracts were washed with brine (110 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was separated via column chromatography (1:1; Et2O/Pet. ether)

Sources & evidence

ORD record
ord-2f7a205155c042f6ad0d4592159964c3
Source dataset
uspto-grants-2009_06
Patent number
US07550469B2

Reaction notes

Loading…