Sodium hydride → 5,5,8,8-Tetramethyl-3-(pyrimidin-2-yl-thio)-5,6,7,8-tetrahydro-2-naphthaldehyde

HRID 1836886Notes

Reaction equation

HRID 1836886 reaction equation
[SH:1][C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].F[C:11]1[C:12]([CH:25]=[O:26])=[CH:13][C:14]2[C:15]([CH3:24])([CH3:23])[CH2:16][CH2:17][C:18]([CH3:22])([CH3:21])[C:19]=2[CH:20]=1>CN(C)C=O>[CH3:21][C:18]1([CH3:22])[CH2:17][CH2:16][C:15]([CH3:23])([CH3:24])[C:14]2[CH:13]=[C:12]([CH:25]=[O:26])[C:11]([S:1][C:2]3[N:7]=[CH:6][CH:5]=[CH:4][N:3]=3)=[CH:20][C:19]1=2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 234989783-Fluoro-2-formyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthaleneHCID 178418793HCID 178418793, compound

Product 1

HCID 234989335,5,8,8-Tetramethyl-3-(pyrimidin-2-yl-thio)-5,6,7,8-tetrahydro-2-naphthaldehydeYield 16%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.479 g (4.27 mmol) of 2-mercaptopyrimidine in 11 mL dimethylformamide was added 0.108 g (4.27 mmol) of 95% sodium hydride. After 20 minutes, 1.00 g (4.27 mmol) of 3-fluoro-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthaldehyde was added and the resulting solution was heated at reflux. After 18 hours, the reaction mixture was cooled to room temperature and partitioned between ethyl acetate and water. The organic phase was washed with water, brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The product was purified by flash chromatography on silica (15% ethyl acetate/hexane) to afford 0.219 g (16%) of 5,5,8,8-tetramethyl-3-(pyrimidin-2-yl-thio)-5,6,7,8-tetrahydro-2-naphthaldehyde (mp=143.2-145.8). Horner-Emmons olefination, followed by ester saponification gave 4-{(E)-2-[5,5,8,8-Tetramethyl-3-(mercaptopyrmidin-2-yl)-5,6,7,8-tetrahydro-naphthalen-2-yl)vinyl]benzoic acid 155 (mp=283-283.5). Substitution of 2-mercaptopyrimidine with 2-mercaptothiazole gave 4-{(E)-2-[5,5,8,8-Tetramethyl-3-(mercaptothiazol-2-yl)-5,6,7,8-tetrahydro-naphthalen-2-yl)vinyl]benzoic acid 154 (MH+=450).

Workup

  1. temperaturethe resulting solution was heated
  2. temperatureat reflux
  3. waitAfter 18 hours
  4. custompartitioned between ethyl acetate and water
  5. washThe organic phase was washed with water, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe product was purified by flash chromatography on silica (15% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a4333ca47f3940059ef3153446776355
Source dataset
uspto-grants-2004_08
Patent number
US06777418B2

Reaction notes

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