Methyl iodide → HCID 66684293, compound

HRID 579175Notes

Reaction equation

HRID 579175 reaction equation
[CH:1](NC(C)C)(C)C.[Li][CH2:9]CCC.[C:13]([Si:17]([CH3:45])([CH3:44])[O:18][CH2:19][CH2:20][CH2:21][CH:22]1[O:27][CH2:26][CH:25]([CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)[N:24]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[C:23]1=[O:43])([CH3:16])([CH3:15])[CH3:14].CI>C1COCC1>[C:13]([Si:17]([CH3:45])([CH3:44])[O:18][CH2:19][CH2:20][CH2:21][C@:22]1([CH3:1])[O:27][CH2:26][CH:25]([CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)[N:24]([CH2:34][C:35]2[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=2)[C:23]1=[O:43])([CH3:14])([CH3:15])[CH3:16].[C:13]([Si:17]([CH3:45])([CH3:44])[O:18][CH2:19][CH2:20][CH2:21][C@@:22]1([CH3:9])[O:27][CH2:26][CH:25]([CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)[N:24]([CH2:34][C:35]2[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=2)[C:23]1=[O:43])([CH3:14])([CH3:15])[CH3:16]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 666846652-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-5-cyclohexyl-4-(4-methoxy-benzyl)-morpholin-3-oneHCID 178418339Butyllithium

Product 2

HCID 66684293HCID 66684293, compoundHCID 66684309HCID 66684309, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of diisopropyl amine (138 mg, 1.36 mmol, 1.3 equiv) in THF (6.0 mL) at −78° C. was added n-BuLi (0.79 mL, 1.6 mL in heptane, 1.26 mmol, 1.2 equiv) and the resulting solution was stirred at −78° C. for 10 minutes. To the solution was added a solution of 2-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-5-cyclohexyl-4-(4-methoxy-benzyl)-morpholin-3-one (500 mg, 1.05 mmol, 1.0 equiv) in THF (2 mL) and the solution was stirred at −78° C. for 30 mins. MeI was added and the solution was stirred at −78° C. for 1 hour then slowly warmed to room temperature over 2 hours. The reaction was quenched by addition of sat. aq. NH4Cl solution. The mixture was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography, EtOAc/heptane 20% to give product (S)-2-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-5-cyclohexyl-4-(4-methoxy-benzyl)-2-methyl-morpholin-3-one 110 mg and product (R)-2-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-5-cyclohexyl-4-(4-methoxy-benzyl)-2-methyl-morpholin-3-one 205 mg.

Workup

  1. stirringthe solution was stirred at −78° C. for 30 mins
  2. stirringthe solution was stirred at −78° C. for 1 hour
  3. temperaturethen slowly warmed to room temperature over 2 hours
  4. customThe reaction was quenched by addition of sat. aq. NH4Cl solution
  5. extractionThe mixture was extracted with EtOAc
  6. washThe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography, EtOAc/heptane 20%

Sources & evidence

ORD record
ord-f7c5c5b36d8b42729af3228d14c03a48
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

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