Potassium Carbonate → Cyclohexylmethyl 5-chlorothiophene-2-carboxylate

HRID 63300

Reaction equation

HRID 63300 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]([OH:9])=[O:8])=[CH:4][CH:3]=1.[CH:10]1([CH2:16]Br)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.C(=O)([O-])[O-].[K+].[K+]>O>[Cl:1][C:2]1[S:6][C:5]([C:7]([O:9][CH2:16][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)=[O:8])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 950485-Chloro-2-thiophenecarboxylic acidHCID 137636Cyclohexane, (bromomethyl)-

Product 1

HCID 84819867Cyclohexylmethyl 5-chlorothiophene-2-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 5-chlorothiophene-2-carboxylic acid (3.01 g, 19.0 mmol), cyclohexylmethyl bromide (3.51 g, 19.8 mmol) and potassium carbonate (2.81 g, 20.33 mmol) was stirred under Ar at +85° C. for 3 days and cooled to room temperature. Reaction mixture was diluted with water and extracted with hexanes three times. Combined organic layers were dried over anhydrous MgSO4 and concentrated under reduced pressure. Purification by flash chromatography (2%-15% EtOAc—hexanes gradient) gave cyclohexylmethyl 5-chlorothiophene-2-carboxylate as a colorless oil. Yield (4.76 g, 97%); 1H NMR (400 MHz, CDCl3) δ 7.56-7.60 (m, 1H), 6.90-6.94 (m, 1H), 4.08 (d, J=6.10 Hz, 2H), 1.64-1.82 (m, 6H), 1.10-1.34 (m, 3H), 0.97-1.10 (m, 2H).

Workup

  1. customReaction mixture
  2. extractionextracted with hexanes three times
  3. dry with materialCombined organic layers were dried over anhydrous MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash chromatography (2%-15% EtOAc—hexanes gradient)

Sources & evidence

ORD record
ord-30c4ccd6c9304edebef711969c425c30
Source dataset
uspto-grants-2016_09
Patent number
US09447078B2

Linked notes

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