Methyl iodide → HCID 68000743, compound

HRID 932041Notes

Reaction equation

HRID 932041 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.[Cl:13][C:14]1[CH:15]=[C:16]([C@H:20]2[CH2:25][C@H:24]([CH2:26][CH:27]=[CH2:28])[S:23][N:22]([CH:29]([CH3:31])[CH3:30])[C@@H:21]2[C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=2)[CH:17]=[CH:18][CH:19]=1.CI.[Li+].CC([N-]C(C)C)C>C1COCC1>[Cl:13][C:14]1[CH:15]=[C:16]([C@H:20]2[CH2:25][C@:24]([CH3:1])([CH2:26][CH:27]=[CH2:28])[S:23][N:22]([CH:29]([CH3:31])[CH3:30])[C@@H:21]2[C:32]2[CH:33]=[CH:34][C:35]([Cl:38])=[CH:36][CH:37]=2)[CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 5

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 67998913HCID 67998913, compoundHCID 178418339Butyllithium

Product 1

HCID 68000743HCID 68000743, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a degassed solution of diisopropylamine (300 μL, 2.123 mmol) in THF (1.0 ml) was added dropwise at −78° C. n-butyllithium, 2.5 M in hexanes (800 μL, 2.000 mmol). After stirring the solution at −78° C. for 10 min, the reaction was warmed to room temperature. In a separate flask, a degassed solution of 111.9 mg (0.255 mmol) of (3S,4R,6R)-4-(3-chlorophenyl)-3-(4-chlorophenyl)-2-(2-propanyl)-6-(2-propen-1-yl)-1,2-thiazinan (Example 117, Step E) and methyl iodide (0.6 ml, 9.62 mmol) in THF (1.0 ml) was heated to 50° C. After five minutes, the LDA solution was added dropwise to the other flask, and stirring continued for 14 hours at 50° C. Upon cooling to room temperature, the reaction was quenched with water (3 mL), then concentrated under reduced pressure. Purification by reverse-phase preparative HPLC using an Agilent Eclipse Plus C18 column (Agilent Technologies, Santa, Clara, Calif.), 0.1% TFA in CH3CN/H2O, gradient 60% to 80% over 25 minutes provided the title compound as a white solid.

Workup

  1. temperaturethe reaction was warmed to room temperature
  2. waitAfter five minutes
  3. stirringstirring
  4. waitcontinued for 14 hours at 50° C
  5. temperatureUpon cooling to room temperature
  6. customthe reaction was quenched with water (3 mL)
  7. concentrationconcentrated under reduced pressure
  8. customPurification by reverse-phase preparative HPLC
  9. customover 25 minutes

Sources & evidence

ORD record
ord-f3bb8c4c3e34445e9c73e8b7ac2d1586
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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