Methyl iodide → HCID 59253277, compound

HRID 386915Notes

Reaction equation

HRID 386915 reaction equation
[CH3:1][C:2]([C:12]1[CH:16]=[C:15]([NH:17][C:18](=[O:32])[C:19]([CH3:31])([S:21]([CH2:24][CH:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)(=[O:23])=[O:22])[CH3:20])[O:14][N:13]=1)([CH3:11])[CH2:3][O:4][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][O:6]1.[CH2:33]([Li])CCC.CI>C1COCC1>[CH3:11][C:2]([C:12]1[CH:16]=[C:15]([NH:17][C:18](=[O:32])[C:19]([CH3:31])([S:21]([CH:24]([CH:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[CH3:33])(=[O:23])=[O:22])[CH3:20])[O:14][N:13]=1)([CH3:1])[CH2:3][O:4][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][O:6]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 59253303HCID 59253303, compoundHCID 178418339Butyllithium

Product 1

HCID 59253277HCID 59253277, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 0.4 g (0.85 mmol) of N-{3-[1,1-dimethyl-2-(tetrahydro-pyran-2-yloxy)-ethyl]-isoxazol-5-yl}-2-methyl-2-(tetrahydro-pyran-4-ylmethanesulfonyl)-propionamide (synthesized according to method B, step 1) in anhydrous THF (5 mL) under nitrogen is cooled to −78° C. A 2.5 M solution of n-butyl lithium in hexanes (1 mL) is added dropwise. The reaction mixture is stirred at −78° C. for 1 h, followed by addition of 0.11 mL (1.69 mmol) of methyl iodide. The reaction is allowed to warm to room temperature and stirred for 18 h. The mixture is quenched by addition of water (5 mL) and the organic solvent is removed under reduced pressure. The aqueous residue is extracted with DCM (2×10 mL). The combined organic extracts are washed with brine (10 mL), dried (Na2SO4) and filtered. The filtrate is concentrated under reduced pressure and the residue is purified by mass-triggered preparative LC (neutral method) to afford 0.1 g of N-{3-[1,1-dimethyl-2-(tetrahydro-pyran-2-yloxy)-ethyl]-isoxazol-5-yl}-2-methyl-2-[1-(tetrahydro-pyran-4-yl)-ethanesulfonyl]-propionamide. Yield: 24%, ES-MS: 403 [M+H].

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 18 h
  3. customThe mixture is quenched by addition of water (5 mL)
  4. customthe organic solvent is removed under reduced pressure
  5. extractionThe aqueous residue is extracted with DCM (2×10 mL)
  6. washThe combined organic extracts are washed with brine (10 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationThe filtrate is concentrated under reduced pressure
  10. customthe residue is purified by mass-triggered preparative LC (neutral method)

Sources & evidence

ORD record
ord-786a734c75d44ba680c02bd7dba1334b
Source dataset
uspto-grants-2013_02
Patent number
US08372874B2

Reaction notes

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