Phenethyl bromide → methyl 4-(phenethylthio)-1H-pyrrole-2-carboxylate

HRID 1987922Notes

Reaction equation

HRID 1987922 reaction equation
[OH-].[Na+].[CH3:3][O:4][C:5]([C:7]1[NH:8][CH:9]=[C:10]([S:12][C:13]#N)[CH:11]=1)=[O:6].BrC[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O.CC(O)(C)C>[CH2:13]([S:12][C:10]1[CH:11]=[C:7]([C:5]([O:4][CH3:3])=[O:6])[NH:8][CH:9]=1)[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 7666Phenethyl bromideHCID 14798Sodium HydroxideHCID 146848292-Methoxycarbonyl-4-thiocyanopyrrole

Product 1

HCID 67215046methyl 4-(phenethylthio)-1H-pyrrole-2-carboxylateYield 85.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of sodium hydroxide (88.0 mg, 2.20 mmol) in degassed H2O (0.500 mL) was added to a mixture of 2-methoxycarbonyl-4-thiocyanopyrrole (0.200 g, 1.10 mmol), prepared according to the procedure described in J. Chem. Soc. Perkin Trans. 2 1990, 699, and (2-bromoethyl)benzene (0.165 mL, 1.21 mmol) in degassed t-BuOH (2.0 mL). The reaction mixture was stirred at 60° C. for 2 h, cooled to rt and concentrated. The residue was dissolved in CH2Cl2 (50 mL) washed with H2O (2×25 mL), dried over anhydrous Na2SO4, concentrated and purified by chromatography on silica gel with MeOH and CH2Cl2 (0-10% gradient) as the mobile phases to afford 0.247 g of the title compound as a light yellow oil: 1H NMR (500 MHz, CDCl3) δ 2.83-2.88 (m, 2H), 2.89-2.95 (m, 2H), 3.87 (s, 3H), 6.94-6.97 (m, 1H), 7.00 (dd, J=2.7, 1.6 Hz, 1H), 7.14-7.22 (m, 3H), 7.26-7.30 (m, 2H), 9.30 (br. s., 1H); HPLC a) column: Phenomenex Luna 5μ 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% H3PO4 to 90% MeOH/10% H2O/0.1% H3PO4; 1 min hold, 4 mL/min UV detection at 220 nm, 3.561 min retention time, (>95%); HPLC b) column: Phenomenex Luna C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 1 min hold; 4 mL/min, UV detection at 220 nm, 3.535 min retention time; MS (ES) 262 [M+H]+.

Workup

  1. customprepared
  2. temperaturecooled to rt
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in CH2Cl2 (50 mL)
  5. washwashed with H2O (2×25 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. custompurified by chromatography on silica gel with MeOH and CH2Cl2 (0-10% gradient) as the mobile phases

Sources & evidence

ORD record
ord-0c578cca3b87443dbb6e8d3a8b6b04d4
Source dataset
uspto-grants-2009_06
Patent number
US07553836B2

Reaction notes

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