Iodoethane → HCID 178436958, compound

HRID 1245607Notes

Reaction equation

HRID 1245607 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[NH:18][NH:17][C:16](=[O:19])[C:15]=2[CH3:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C)[CH2:23][CH2:24]N(C)C.C([Li])CCC.C(I)C>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:15]([CH2:23][CH3:24])([CH3:20])[C:16]([OH:19])=[N:17][N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6340IodoethaneHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 21912822HCID 21912822, compoundHCID 178418339Butyllithium

Product 1

HCID 178436958HCID 178436958, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 255 mg (0.9 mmol) of 1-tert-butoxycarbonyl-4-(4-methyl-(1H)-pyrazol-3-one-5-yl)piperidine (from Piperidine 15, Step C) and 0.155 mL (1.0 mmol) of freshly distilled tetramethylethylene diamine in 3 mL of THF at −78° C. was treated with 0.8 mL (2.0 mmol) of 2.5 M n-butyl lithium in hexanes (J. Med. Chem. 1996, 39, 3920–3928). After stirring for 15 minutes at −78° C., the reaction was warmed to 0° C. for 15 minutes. Upon recooling to −78° C., 0.11 mL (1.3 mmol) of ethyliodide was added. After warming to rt and stirring for 19 hours, the reaction was cooled to 0° C. and quenched with 1 N HCl. The reaction mixture was partitioned between 100 mL of EtOAc and 100 mL of 1 N HCl. After separating phases, the organic layer washed with 100 mL of brine, dried over Na2SO4 and concentrated. The residue was purified by flash chromatography using 99:1 v/v CH2Cl2/MeOH, 98:2 v/v CH2Cl2/MeOH and 97:3 v/v CH2Cl2/MeOH as the gradient to afford the title compound as a white solid: RF: 0.40 (19:1 v/v CH2Cl2/MeOH); 1H-NMR (500 MHz) δ 0.73 (t, J=7.4, 3H), 1.26 (s, 3H), 1.47 (s, 9H), 1.59–1.85 (m, 6H), 2.38 (m, 1H), 2.76–2.81 (m, 2H), 4.16–4.21 (m, 2H), 8.61 (br s, 1H).

Workup

  1. temperaturethe reaction was warmed to 0° C. for 15 minutes
  2. customUpon recooling to −78° C.
  3. temperatureAfter warming to rt
  4. stirringstirring for 19 hours
  5. temperaturethe reaction was cooled to 0° C.
  6. customquenched with 1 N HCl
  7. customThe reaction mixture was partitioned between 100 mL of EtOAc and 100 mL of 1 N HCl
  8. customAfter separating phases
  9. washthe organic layer washed with 100 mL of brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated
  12. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-ce6c0ec5ee5c4e51b47643e73592f4d6
Source dataset
uspto-grants-2006_10
Patent number
US07125887B2

Reaction notes

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