Methyl iodide → HCID 58641347, compound

HRID 1394957Notes

Reaction equation

HRID 1394957 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[C:19]1[CH2:23][N:22]([CH2:24][CH2:25][S:26]([CH2:29][CH3:30])(=[O:28])=[O:27])[C@H:21]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:20]=1.I[CH3:38]>C1COCC1>[F:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[C:19]1[CH2:23][N:22]([CH2:24][CH:25]([S:26]([CH2:29][CH3:30])(=[O:27])=[O:28])[CH3:38])[C@H:21]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:20]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 58641378HCID 58641378, compound

Product 1

HCID 58641347HCID 58641347, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of lithium bis(trimethylsilyl)amide in THF (1.0 M, 0.74 mL, 0.74 mmol, 4.0 equiv) was added to a solution of (2S)-4-(2,5-difluorophenyl)-1-[2-(ethylsulfonyl)ethyl]-2-phenyl-2,5-dihydro-1H-pyrrole (70 mg, 0.185 mmol, 1 equiv) in THF (5 mL) at −78° C., then stirred for 1 h. Iodomethane (0.035 mL, 0.56 mmol, 3.0 equiv) was added and the resulting mixture was warmed to 0° C. and stirred for 30 minutes. The mixture was then partitioned between saturated potassium bisulfate solution and ethyl acetate (2×40 mL). The combined organic layers were dried over magnesium sulfate and were concentrated. The residue was purified by flash column chromatography (CH2Cl2 initially, grading to 4% EtOAc in CH2Cl2) to give (2S)4 (2,5-difluorophenyl)-1-[2-(ethylsulfonyl)propyl]-2-phenyl-2,5-dihydro-1H-pyrrole (38-1) as a single diastereomer (colorless oil). 1H NMR (500 M, CDCl3) δ 7.38-7.28 (m, 5H), 7.08-6.92 (m, 3H), 6.29 (br s, 1H), 4.66 (br s), 4.37 (dd, 1H, J=12.5, 4.9 Hz), 3.84 (br d, 1H, J=13.0 Hz), 3.36 (dd, 1H, J=13.7, 7.1 Hz), 2.99 (m, 1H), 2.84 (m, 2H), 2.77 (dd, 1H, J=13.9, 7.3 Hz), 1.31 (d, 3H, J=7.1 Hz), 1.19 (t, 3H, J=7.6 Hz). LRMS m/z (M+H) 392.4 found, 392.1 required.

Workup

  1. stirringstirred for 30 minutes
  2. customThe mixture was then partitioned between saturated potassium bisulfate solution and ethyl acetate (2×40 mL)
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. concentrationwere concentrated
  5. customThe residue was purified by flash column chromatography (CH2Cl2 initially

Sources & evidence

ORD record
ord-06d6b52915f74c8585e40cd68fc32f04
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

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