Ethyl Acetate → 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-hydroxymethyl-1-methylprop-2-ynyl)-2-methylsulfanyl acetamide

HRID 1962871Notes

Reaction equation

HRID 1962871 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C([SiH2][O:24][C:25](C1C=CC=CC=1)(C1C=CC=CC=1)[C:26]([NH:30][C:31](=[O:48])[CH:32]([O:35][C:36]1[CH:37]=[C:38]2[C:43](=[CH:44][CH:45]=1)[N:42]=[CH:41][C:40]([C:46]#[CH:47])=[CH:39]2)[S:33][CH3:34])([CH3:29])[C:27]#[CH:28])(C)(C)C.C(OCC)(=O)C>C1COCC1.[Cl-].[Na+].O>[C:46]([C:40]1[CH:41]=[N:42][C:43]2[C:38]([CH:39]=1)=[CH:37][C:36]([O:35][CH:32]([S:33][CH3:34])[C:31]([NH:30][C:26]([CH2:25][OH:24])([CH3:29])[C:27]#[CH:28])=[O:48])=[CH:45][CH:44]=2)#[CH:47]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 178437010HCID 178437010, compound

Product 1

HCID 595653502-(3-ethynyl-quinolin-6-yloxy)-N-(1-hydroxymethyl-1-methylprop-2-ynyl)-2-methylsulfanyl acetamideYield 72.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of tetrabutylammonium fluoride (1 M) in THF was added dropwise to a solution of N-[1-(tert-butyl-diphenyl-silanyloxymethyl)-1-methyl-prop-2-ynyl]-2-(3-ethynyl-quinolin-6-yloxy)-2-methylsulfanyl-acetamide (1.49 g) at 0° C. The reaction mixture was allowed to warm up to room temperature, stirred for 1.5 h and then poured onto a mixture of ethyl acetate and brine. The two layers were separated and the aqueous layer was extracted thrice with ethyl acetate. The organic layers were combined, washed once with brine and then dried over sodium sulphate. After filtration and concentration under reduced pressure 2.47 g of crude material was isolated as a yellow oil which was purified by flash chromatography on silica gel (hexane/ethyl acetate) to provide 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-hydroxymethyl-1-methylprop-2-ynyl)-2-methylsulfanyl acetamide as a white solid (0.646 g, m.p.=149-150° C.) which was used directly in Stage 6 described below.

Workup

  1. customThe two layers were separated
  2. extractionthe aqueous layer was extracted thrice with ethyl acetate
  3. washwashed once with brine
  4. dry with materialdried over sodium sulphate
  5. filtrationAfter filtration and concentration under reduced pressure 2.47 g of crude material
  6. customwas isolated as a yellow oil which
  7. customwas purified by flash chromatography on silica gel (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-6e73ddcfdf924331a0c0e320a07e9199
Source dataset
uspto-grants-2013_04
Patent number
US08415272B2

Reaction notes

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