Triethylamine → HCID 118659579, compound

HRID 1477244Notes

Reaction equation

HRID 1477244 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[CH:9]=[C:8]([C:10]([OH:12])=[O:11])[S:7][C:6]=2[CH:13]=1.[C:14]([C@@H:16]1[CH2:18][C@H:17]1[CH2:19][OH:20])#[CH:15].C(N(CC)CC)C>CN(C=O)C.[Cu]I.[Cl-].[Cl-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd+2]>[OH:20][CH2:19][C@@H:17]1[CH2:18][C@H:16]1[C:14]#[C:15][C:2]1[CH:3]=[CH:4][C:5]2[CH:9]=[C:8]([C:10]([OH:12])=[O:11])[S:7][C:6]=2[CH:13]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 135679806-Bromo-1-benzothiophene-2-carboxylic acidHCID 129387989HCID 129387989, compound

Product 1

HCID 118659579HCID 118659579, compoundYield 85%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 84124Bis(triphenylphosphine)palladium chlorideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of 6-bromobenzo[b]thiophene-2-carboxylic acid (7.1, 1.0 g, 3.9 mmol) in DMF (7.5 mL) under a nitrogen atmosphere were added racemic ((trans)-2-ethynylcyclopropyl)methanol (1.7, 935 mg, 9.7 mmol), copper(I) iodide (30 mg, 0.16 mmol) and palladium(II) bis(triphenylphosphine)dichloride (56 mg, 0.08 mmol), followed by triethylamine (2.5 mL) and the reaction was stirred at room temperature for 1 hr, and then at 40° C. for 20 hr. The reaction mixture was partitioned between 2N aqueous sodium hydroxide and ethyl acetate. The aqueous layer was acidified with conc HCl and extracted with ethyl acetate. The resulting organic layer was washed with water, saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 6-(((trans)-2-(hydroxymethyl)cyclopropyl)ethynyl)benzo[b]thiophene-2-carboxylic acid (7.2, 900 mg, 3.3 mmol, 85%).

Workup

  1. waitat 40° C. for 20 hr
  2. customThe reaction mixture was partitioned between 2N aqueous sodium hydroxide and ethyl acetate
  3. extractionextracted with ethyl acetate
  4. washThe resulting organic layer was washed with water, saturated sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-16cedf78bf634d3593594d1daa32a7e7
Source dataset
uspto-grants-2016_08
Patent number
US09403758B2

Reaction notes

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