Tert-butyl-(3-iodopropoxy)-dimethylsilane → 2-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-5-cyclohexyl-4-(4-methoxy-benzyl)-morpholin-3-one

HRID 579172Notes

Reaction equation

HRID 579172 reaction equation
[CH:1]1([CH:7]2[N:12]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[C:11](=[O:22])[CH2:10][O:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Li]CCCC.[C:28]([Si:32]([O:35][CH2:36][CH2:37][CH2:38]I)([CH3:34])[CH3:33])([CH3:31])([CH3:30])[CH3:29]>C1COCC1>[C:28]([Si:32]([CH3:34])([CH3:33])[O:35][CH2:36][CH2:37][CH2:38][CH:10]1[O:9][CH2:8][CH:7]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[N:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=2)[C:11]1=[O:22])([CH3:31])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 11022956Tert-butyl-(3-iodopropoxy)-dimethylsilaneHCID 666847235-Cyclohexyl-4-(4-methoxy-benzyl)-morpholin-3-oneHCID 178418339Butyllithium

Product 1

HCID 666846652-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-5-cyclohexyl-4-(4-methoxy-benzyl)-morpholin-3-oneYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 5-cyclohexyl-4-(4-methoxy-benzyl)-morpholin-3-one (700 mg, 2.3 mmol, 1.0 equiv) in THF (10.0 mL) at −78° C. was added n-BuLi (1.58 mL, 1.6 M in heptane, 2.54 mmol, 1.1 equiv). The resulting solution was stirred at −78° C. for 30 minutes, after which it was added a solution of tert-Butyl-(3-iodo-propoxy)-dimethyl-silane (693 mg, 2.3 mmol, 1.0 equiv) in THF (1.0 mL). The solution was stirred at −78° C. for 30 minutes and 2 hours at room temperature after which it was quenched by addition of sat. aq. NH4Cl solution. The mixture was extracted with EtOAc. The organic layer was combined, dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography, EtOAc/heptane 30% to give product 480 mg (yield 44%).

Workup

  1. stirringThe solution was stirred at −78° C. for 30 minutes and 2 hours at room temperature after which it
  2. customwas quenched by addition of sat. aq. NH4Cl solution
  3. extractionThe mixture was extracted with EtOAc
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography, EtOAc/heptane 30%

Sources & evidence

ORD record
ord-162c6b4c046f4cf6965bc8bdc1fe3606
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

Loading…