Tributylstannane → HCID 537259, compound

HRID 1780722Notes

Reaction equation

HRID 1780722 reaction equation
[F:1][C:2]([F:30])([CH:8](OC(C(C1NC=CN=1)=O)=S)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[C:3]([O:5][CH2:6][CH3:7])=[O:4].C([SnH](CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[F:1][C:2]([F:30])([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[C:3]([O:5][CH2:6][CH3:7])=[O:4]

Participants

4

Reactant 2

HCID 5948TributylstannaneHCID 19047207HCID 19047207, compound

Product 1

HCID 537259HCID 537259, compoundYield 77.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

Ethyl bromodifluoroacetate (6.0 g) and dodecyl aldehyde (1.84 g) were mixed with anhydrous tetrahydrofuran (40 ml) under argon atmosphere, and the solution was added dropwise to a suspension of zinc powder (2.2 g) and copper bromide (I) (0.22 g) in anhydrous tetrahydrofuran (40 ml) which was heated to a refluxing temperature. The mixture, after heating under reflux for 5 hours, was cooled and concentrated under reduced pressure. The residue was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 20:1 to 10:1) to give ethyl 2,2-difluoro-3-hydroxytetradecanoate (0.92 g). After the mixture of ethyl 2,2-difluoro-3-hydroxytetradecanoate (0.92 g) and 1,1'-thiocarbonyl imidazole (1.26 g) in 1,2-dichloroethane was heated under reflux for 1 hour, it was cooled and concentrated. The residue was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 30:1 to 10:1) to give ethyl 2,2-difluoro-3-imidazoylthiocarbonyloxytetradecanoate (1.32 g). To a solution of ethyl 2,2-difluoro-3-imidazoylthiocarbonyloxytetradecanoate (1.32 g) dissolved in toluene (40 ml) under argon atmosphere, which was heated under reflux, was added dropwise a solution of tri-n-butyltin hydride (2.93 ml) in toluene (70 ml). The mixture, after heating under reflux for 2 hours, was concentrated under reduced pressure. The residue was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 300:1 to 50:1) to give ethyl 2,2-difluorotetradecanoate (0.67 g). To a solution of ethyl 2,2-difluorotetradecanoate (489 mg) in N,N-dimethylformamide (30 ml) were added 6-(4'-N-glycyl-spicaminyl-amino)purine hydrochloride (300 mg) and triethylamine (1.5 ml). The mixture was stirred for 12 hours. After the solvent was evaporated, the residue was subjected to chromatography on a silica gel column with eluent systems of chloroform-methanol-water (from 8.5:1:0.05 to 7:1:0.05) to give SPK182 in the yield of 95 mg.

Workup

  1. temperaturewhich was heated
  2. temperatureunder reflux
  3. temperatureThe mixture, after heating
  4. temperatureunder reflux for 2 hours
  5. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-a2b3187b071449d8bca18e6b39088d1e
Source dataset
uspto-grants-1997_05
Patent number
US05631238

Reaction notes

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