Methyl iodide → HCID 11675645, compound

HRID 1394929Notes

Reaction equation

HRID 1394929 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14]([NH:16][CH:17]2[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]2)=[O:15])[C@H:11]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:10]=1.[H-].[Na+].[CH3:38]I>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14]([N:16]([CH3:38])[CH:17]2[CH2:18][CH2:19][NH:20][CH2:21][CH2:22]2)=[O:15])[C@H:11]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:10]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86605054HCID 86605054, compound

Product 1

HCID 11675645HCID 11675645, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Crude 18-3 (100 mg, 0.2 mmol) was dissolved in anhydrous DMF (3 mL) and cooled to 0° C. under N2. NaH (28 mg, 1.17 mmol) was added neat and the reaction was stirred 30 minutes at 0° C. Following cessation of H2 evolution, MeI (0.15 mL, 2.4 mmol) was added and the reaction was stirred 12 hours at 25° C. Upon completion, the reaction was diluted with EtOAc (10 mL), and the organic layer was washed successively with 5% NH4Cl (1×10 mL), H2O (3×5 mL) and brine (1×10 mL). The organic layer was dried (MgSO4), filtered and concentrated under reduced pressure. The crude oil was dissolved in anhydrous CH2Cl2 (10 mL). The resulting solution was treated with trifluoroacetic acid (5 mL) and stirred 1 hour at 25° C. Upon completion, the reaction was concentrated and directly subjected to reverse-phase column chromatography to provide 18-4: 1H NMR (300 MHz, CD3OD) δ 7.33 (m, 4H), 7.25 (m, 2H), 7.17 (m, 1H), 7.08 (m, 1H), 6.41 (s, 1H), 6.00 (t, J=2.7 Hz, 1H), 5.07 (ddd, J=14.0, 5.6, 1.7 Hz, 1H), 4.55 (d, J=14.0 Hz, 1H), 3.82 (m, 1H), 3.40 (m, 2H), 3.03 (dt, J=12.5, 3.9 Hz, 1H), 2.88 (s, 3H), 2.81 (dt, J=13.1, 2.9 Hz, 1H), 1.90 (m, 4H); LRMS m/z (M+H) 398.0 found, 398.2 required.

Workup

  1. additionwas added
  2. stirringthe reaction was stirred 12 hours at 25° C
  3. washthe organic layer was washed successively with 5% NH4Cl (1×10 mL), H2O (3×5 mL) and brine (1×10 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe crude oil was dissolved in anhydrous CH2Cl2 (10 mL)
  8. additionThe resulting solution was treated with trifluoroacetic acid (5 mL)
  9. stirringstirred 1 hour at 25° C
  10. concentrationUpon completion, the reaction was concentrated
  11. customto provide 18-4

Sources & evidence

ORD record
ord-3ec17a88859d4e5ab4c5a6bcf251468b
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

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