Methyl iodide → HCID 66684080, compound

HRID 579178Notes

Reaction equation

HRID 579178 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:8][C:9]=1[N:10]1[CH:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][O:13][C@H:12]([CH2:22][CH:23]=[CH2:24])[C:11]1=[O:25])=[O:4].[Li+].[CH3:33]C([N-]C(C)C)C.CI>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:8][C:9]=1[N:10]1[C@H:15]([CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)[CH2:14][O:13][C@:12]([CH2:22][CH:23]=[CH2:24])([CH3:33])[C:11]1=[O:25])=[O:4].[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:8][C:9]=1[N:10]1[C@H:15]([CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)[CH2:14][O:13][C@@:12]([CH2:22][CH:23]=[CH2:24])([CH3:33])[C:11]1=[O:25])=[O:4]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 66684866HCID 66684866, compound

Product 2

HCID 66684080HCID 66684080, compoundHCID 66685258HCID 66685258, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-((R)-2-Allyl-5-cyclohexyl-3-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (120 mg, 0.27 mmol, 1.0 equiv) in THF (1.0 mL) at −78° C. was added LDA (0.16 mL, 2.0 M in THF, 0.32 mmol, 1.2 equiv) and the resulting solution was stirred at −78° C. for 20 minutes. To the solution was then added methyliodide (192 mg, 1.35 mmol, 5.0 equiv). The solution was warmed to room temperature and the stirred at this temperature for 30 minutes. 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 25% to give product 3-((2S,5R)-2-Allyl-5-cyclohexyl-2-methyl-3-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester 18 mg and product 3-((2R,5R)-2-Allyl-5-cyclohexyl-2-methyl-3-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester 50 mg.

Workup

  1. temperatureThe solution was warmed to room temperature
  2. stirringthe stirred at this temperature for 30 minutes
  3. customThe reaction was quenched by addition of sat. aq. NH4Cl solution
  4. extractionThe mixture was extracted with EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography, EtOAc/heptane 25%

Sources & evidence

ORD record
ord-e8220a48d4cf425dbb5186f70cf39927
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

Loading…