3-Butyn-1-OL → HCID 9844719, compound

HRID 1978940Notes

Reaction equation

HRID 1978940 reaction equation
Br[C:2]1[S:24][C:5]2[N:6]([CH2:22][CH3:23])[CH:7]=[C:8]([C:11]([NH:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=3)=[O:12])[C:9](=[O:10])[C:4]=2[CH:3]=1.[CH2:25]([OH:29])[CH2:26][C:27]#[CH:28]>C(NCC)C.[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][NH:13][C:11]([C:8]2[C:9](=[O:10])[C:4]3[CH:3]=[C:2]([C:28]#[C:27][CH2:26][CH2:25][OH:29])[S:24][C:5]=3[N:6]([CH2:22][CH3:23])[CH:7]=2)=[O:12])=[CH:16][CH:17]=1

Participants

6

Reactant 2

HCID 135663-Butyn-1-OLHCID 9845342HCID 9845342, compound

Product 1

HCID 9844719HCID 9844719, compoundYield 64%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8021DiethylamineSolvent

Procedure

To a suspension of 2-bromo-N-(4-chlorobenzyl)-7-ethyl-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamide (Example No. 11) (0.500 g) in diethylamine (12 mL) is added copper iodide (0.067 g) and Pd(PPh3)2Cl2 (0.041 g) followed by addition of 3-butyn-1-ol (0.11 mL). The reaction is stirred at rt for 3 d. The diethylamine is removed in vacuo and the resulting residue is partitioned between H2O (50 mL) and CH2Cl2 (50 mL). The organic layer is removed, and the aqueous layer is extracted with CH2Cl2 (3×50 mL). The combined organic layers are washed with a saturated NH4Cl solution (50 mL), dried with MgSO4, filtered, and concentrated in vacuo. The resulting orange solid is purified by column chromatography (CH2Cl2:CH3OH, 98:2). Fractions homogeneous by TLC are combined and concentrated in vacuo. The resulting yellow solid is recrystallized from methanol to yield 0.312 g (64%) of the title compound as a pale yellow, crystalline solid.

Workup

  1. customThe diethylamine is removed in vacuo
  2. customthe resulting residue is partitioned between H2O (50 mL) and CH2Cl2 (50 mL)
  3. customThe organic layer is removed
  4. extractionthe aqueous layer is extracted with CH2Cl2 (3×50 mL)
  5. washThe combined organic layers are washed with a saturated NH4Cl solution (50 mL)
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting orange solid is purified by column chromatography (CH2Cl2:CH3OH, 98:2)
  10. concentrationconcentrated in vacuo
  11. customThe resulting yellow solid is recrystallized from methanol

Sources & evidence

ORD record
ord-92a844f26e9c476180f85f133469dc53
Source dataset
uspto-grants-2001_05
Patent number
US06239142B1

Reaction notes

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