3-Fluorobenzyl bromide → HCID 59161310, compound

HRID 545565Notes

Reaction equation

HRID 545565 reaction equation
[CH3:1][O:2][C:3](=[O:20])[NH:4][CH:5]1[CH2:17][C:16]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:18]#[N:19])[CH:14]=3)[NH:9][C:8]=2[CH2:7][CH2:6]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[F:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH2:35]Br>CN(C)C=O>[CH3:1][O:2][C:3](=[O:20])[NH:4][CH:5]1[CH2:17][C:16]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:18]#[N:19])[CH:14]=3)[N:9]([CH2:35][C:34]3[CH:37]=[CH:38][CH:39]=[C:32]([F:31])[CH:33]=3)[C:8]=2[CH2:7][CH2:6]1

Participants

5

Reactant 3

HCID 680073-Fluorobenzyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 57431678HCID 57431678, compound

Product 1

HCID 59161310HCID 59161310, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Combine (6-cyano-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-carbamic acid methyl ester (460 mg, 1.7 mmol) and anhydrous dimethylformamide (15 mL) under nitrogen. Chill the mixture to 0° C. and add potassium bis(trimethylsilyl)amide (0.5M toluene solution, 3.4 mL, 1.7 mmol). Stir the resulting mixture for 30 minutes, then add 3-fluorobenzyl bromide (210 μL, 1.7 mmol) and stir the reaction mixture for 4 h allowing slow warming to room temperature. Quench the reaction with water (50 mL) and extract the product with ethyl acetate (2×50 mL). Dry the combined extracts with magnesium sulfate and concentrate in vacuo. Purify the product via flash chromatography (25% ethyl acetate/hexanes isocratic) to afford 475 mg (74%) of a white solid. LCMS (Method E): 100% (m/z) 378 (M+1, APCI-pos); 1H NMR (DMSO, 400 MHz): δ 11.33 (s, 1H), 7.85 (s, 1H), 7.46 (d, 1H, J=7.9 Hz), 7.39-7.27 (m, 7H), 5.03 (q, 2H, J=8.8 Hz), 3.87-3.75 (m, 1H), 3.87-3.75 (m, 1H), 2.96 (dd, 1H, J=15.2, 5.1 Hz), 2.85-2.77 (m, 2H), 2.55-2.49 (m, 1H), 2.07-1.97 (m, 1H), 1.85-1.71 (m, 1H).

Workup

  1. temperatureallowing slow warming to room temperature
  2. customQuench
  3. customthe reaction with water (50 mL)
  4. extractionextract the product with ethyl acetate (2×50 mL)
  5. dry with materialDry the combined extracts with magnesium sulfate
  6. concentrationconcentrate in vacuo
  7. customPurify the product via flash chromatography (25% ethyl acetate/hexanes isocratic)

Sources & evidence

ORD record
ord-838c1b542db149a09378ab04581331ae
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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