Methyl iodide → HCID 58817651, compound

HRID 456565Notes

Reaction equation

HRID 456565 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 tertbutoxide (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-543778307ed64892a65ee4fa8ab44206
Source dataset
uspto-grants-2007_03
Patent number
US07186724B2

Reaction notes

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