1,1-Dibromoethane → HCID 59752338, compound

HRID 749396Notes

Reaction equation

HRID 749396 reaction equation
Br[CH:2](Br)C.[CH3:5][O:6][C:7]([C:9]1[S:10][C:11]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:12][C:13]=1[N:14]([C:22]([CH:24]1[CH2:29][CH2:28][CH:27]([CH3:30])[CH2:26][CH2:25]1)=[O:23])[CH:15]1[CH2:20][CH2:19][C:18](=O)[CH2:17][CH2:16]1)=[O:8].C(=O)(O)[O-].[Na+]>O1CCCC1.ClCCl.[Zn]>[CH3:5][O:6][C:7]([C:9]1[S:10][C:11]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:12][C:13]=1[N:14]([C:22]([CH:24]1[CH2:25][CH2:26][CH:27]([CH3:30])[CH2:28][CH2:29]1)=[O:23])[CH:15]1[CH2:20][CH2:19][C:18](=[CH2:2])[CH2:17][CH2:16]1)=[O:8]

Participants

7

Reactant 3

HCID 112011,1-DibromoethaneHCID 516892Sodium BicarbonateHCID 597523053-[(4-Methyl-cyclohexanecarbonyl)-(4-oxo-cyclohexyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 59752338HCID 59752338, compoundYield 81%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

To a suspension of zinc dust (2.87 g, 44.0 mmol) and dibromoethane (1.00 mL, 14.4 mmol) in tetrahydrofuran (20 mL) stirred under a nitrogen atmosphere at −40° C. was added titane tetrachloride (10 mL of a solution 1M in dichloromethane, 10 mmol). The mixture was then allowed to warm to room temperature and was stirred for two days at this temperature. This methylation reagent (2.5 eq) was added to a solution of 3-[(4-Methyl-cyclohexanecarbonyl)-(4-oxo-cyclohexyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (0.200 g, 0.440 mmol, 1 eq) in dichloromethane (2 mL) and the resulting mixture was stirred 3 h at room temperature. A saturated solution of sodium bicarbonate was then added and reaction mixture was extracted with dichloromethane (3×30 mL). Organic phases were combined, dried over sodium sulfate and concentrated. The crude was purified by chromatography (30% ethyl acetate/hexanes) to give 160 mg (81%) of 3-[(4-Methyl-cyclohexanecarbonyl)-(4-methylene-cyclohexyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester as a white solid. NMR 1H (CDCl3, 400 MHz) 7.63 ppm (d, 2H); 7.40 ppm (m, 3H); 6.98 ppm (s, 1H); 4.82 ppm (tt, 1H); 4.78 ppm (d, 2H); 3.85 ppm (s, 3H); 2.20 ppm (m, 4H); 2.05 ppm (m, 2H); 1.90 ppm (d, 1H); 1.65 ppm (m, 4H); 1.42 ppm (m, 1H); 1.30 ppm (m, 2H); 1.00 ppm (m, 2H); 0.78 ppm (d, 3H); 0.64 ppm (m, 2H).

Workup

  1. temperatureto warm to room temperature
  2. stirringwas stirred for two days at this temperature
  3. stirringthe resulting mixture was stirred 3 h at room temperature
  4. customreaction mixture
  5. extractionwas extracted with dichloromethane (3×30 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe crude was purified by chromatography (30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-5102690302464d1f974e123bf1a21929
Source dataset
uspto-grants-2008_07
Patent number
US07402608B2

Reaction notes

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