Methyl iodide → HCID 67920426, compound

HRID 1110653Notes

Reaction equation

HRID 1110653 reaction equation
[CH:1](NC1CCCCC1)(C)C.[Li]CCCC.[CH:16]1[C:27]2[CH2:26][C:25]3[CH:28]=[CH:29][CH:30]=[CH:31][C:24]=3[O:23][CH:22]([C:32]([O:34][CH3:35])=[O:33])[O:21][C:20]=2[CH:19]=[CH:18][CH:17]=1.CI>O1CCCC1.CS(C)=O.C(Cl)Cl>[CH3:35][O:34][C:32]([C:22]1([CH3:1])[O:21][C:20]2[CH:19]=[CH:18][CH:17]=[CH:16][C:27]=2[CH2:26][C:25]2[CH:28]=[CH:29][CH:30]=[CH:31][C:24]=2[O:23]1)=[O:33]

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 62386CyclohexylisopropylamineHCID 22153860HCID 22153860, compoundHCID 178418339Butyllithium

Product 1

HCID 67920426HCID 67920426, compoundYield 47.5%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of isopropyl cyclohexyl amine (2.92 ml, 0.0178 mol) in 15 ml of dry tetrahydrofuran (THF) under N2 at 0° C. is added n-BuLi (11.84 ml of 1.5 M in hexane). After stirring 15 minutes at 0° C., the solution is cooled to -65° C. and a solution of methyl 12H-dibenzo[d,g][1,3]dioxocin-6-carboxylate (4.0 g, 0.0148 mol) in 10 ml of THF is added dropwise over a period of 5 minutes. The solution is stirred at -65° C. for an additional 10 minutes and then added via syringe over a period of 2 minutes to a solution of methyl iodide (1.84 ml, 0.0246 mol) in 25 ml of dry dimethyl sulfoxide at room temperature After stirring for 30 minutes, the reaction mixture is diluted with 300 ml of CH2Cl2, washed with H2O, 1N HC1 and then brine, dried over MgSO4 and concentrated. The residue obtained is purified by dry column chromatography (elution with 1:4 ethyl acetate-hexanes) to afford 2 g of a yellow syrup. This material was subjected to HPLC purification (Waters 500, 2 columns, 4 cycles, elution with 1:7 ethylacetatehexanes) to afford 1.1 g (26 percent) of product as a clear sirup: IR (neat) 5.65, 6.3, 6.7, 6.85, 7.25 cm-1 ; 1H NMR (60 MHz, CDCl3) δ 1.36 (s, 3, CH3), 3.71 and 4.32 (2d, 2, CH2) 3.9 (s, 3, OCH3), 6.95-7.4 (m, 8, Ar--H).

Workup

  1. temperaturethe solution is cooled to -65° C.
  2. stirringThe solution is stirred at -65° C. for an additional 10 minutes
  3. stirringAfter stirring for 30 minutes
  4. washwashed with H2O, 1N HC1
  5. dry with materialbrine, dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue obtained
  8. customis purified
  9. customby dry
  10. washcolumn chromatography (elution with 1:4 ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-ae815131edbb45cf964d77084d872e24
Source dataset
uspto-grants-1990_12
Patent number
US04976770

Reaction notes

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