Methyl iodide → HCID 58392467, compound

HRID 561397Notes

Reaction equation

HRID 561397 reaction equation
[CH:1]([N-]C(C)C)(C)C.[Li+].[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]([C:23]2[C:31]3[C:26](=[C:27]([CH2:32][S:33][CH3:34])[CH:28]=[CH:29][CH:30]=3)[N:25]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH:24]=2)[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:12]([F:42])[CH:11]=1.CI>O1CCCC1.ClCCl>[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]([C:23]2[C:31]3[C:26](=[C:27]([CH2:32][S:33][CH3:34])[CH:28]=[CH:29][CH:30]=3)[N:25]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH:24]=2)[CH:17]([CH3:1])[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:12]([F:42])[CH:11]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 58392200HCID 58392200, compound

Product 1

HCID 58392467HCID 58392467, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

3.55 ml (7.10 mmol) of a 2N solution of lithium diisopropylamide in tetrahydrofuran were introduced into 40 ml of absolute tetrahydrofuran at −78° C., a solution of 3.00 g (5.93 mmol) of the compound from Example 35A in 20 ml of tetrahydrofuran was added, and the mixture was stirred for 1 h. 1.01 g (7.11 mmol) of methyl iodide were added at −78° C., and the reaction mixture was warmed to RT. It was then diluted with dichloromethane, the phases were separated, and the organic phase was washed with 1N hydrochloric acid, dried over magnesium sulfate, filtered and concentrated. The crude product was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 2.45 g (80% of theory) of the title compound as mixture of diastereomers.

Workup

  1. customthe phases were separated
  2. washthe organic phase was washed with 1N hydrochloric acid
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid)

Sources & evidence

ORD record
ord-46f1fef6d3a248adb209ddb82b61724d
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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