Cyclohexanemethanol → Cyclohexylmethyl 4-(cyclohexylmethoxy)thiophene-2-carboxylate

HRID 63316

Reaction equation

HRID 63316 reaction equation
[CH:1]1([CH2:7][OH:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[C:12]1[CH:13]=[C:14]([C:17]([O:19][CH2:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:18])[S:15][CH:16]=1.[NH4+].[Cl-]>C1COCC1.[Cu]I>[CH:1]1([CH2:7][O:8][C:12]2[CH:13]=[C:14]([C:17]([O:19][CH2:20][CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)=[O:18])[S:15][CH:16]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 7507CyclohexanemethanolHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 86694606Cyclohexylmethyl 4-bromothiophene-2-carboxylate

Product 1

HCID 86694607Cyclohexylmethyl 4-(cyclohexylmethoxy)thiophene-2-carboxylate

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

Cyclohexylmethanol (0.50 mL, 4.06 mmol) was added to a suspension of NaH (0.080 g, 3.33 mmol) in anhydrous THF (5 mL). Then cyclohexylmethyl 4-bromothiophene-2-carboxylate (0.56 g, 1.847 mmol) was added to the reaction mixture followed by CuI (0.34 g, 1.79 mmol). The reaction mixture was stirred at room temperature for 12 days then aqueous NH4Cl (25%) was added. Aqueous layer was extracted with EtOAc and combined organic layers were washed with brine, dried over anhydrous MgSO4 and concentrated under reduced pressure. Flash chromatography purification (2%-10% EtOAc—hexanes gradient) gave cyclohexylmethyl 4-(cyclohexylmethoxy)thiophene-2-carboxylate as a colorless oil. Yield (0.17 g, 27%); 1H NMR (400 MHz, CD3OD) δ 7.35 (d, J=1.7 Hz, 1H), 6.75 (d, J=1.7 Hz, 1H), 4.07 (d, J=6.3 Hz, 2H), 3.78 (d, J=6.3 Hz, 2H), 1.65-1.90 (m, 12H), 1.15-1.38 (m, 6H), 1.00-1.15 (m, 4H).

Workup

  1. extractionAqueous layer was extracted with EtOAc
  2. washwere washed with brine
  3. dry with materialdried over anhydrous MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customFlash chromatography purification (2%-10% EtOAc—hexanes gradient)

Sources & evidence

ORD record
ord-198b10e8e72d497abae75e380763bb01
Source dataset
uspto-grants-2016_09
Patent number
US09447078B2

Linked notes

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