(2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxo-tetrahydro-2H-pyran-2-carbaldehyde → (4R,6S)-4-(tert-butyldimethylsilyloxy)-6-(dihydroxymethyl)-tetrahydropyran-2-one

HRID 1928686Notes

Reaction equation

HRID 1928686 reaction equation
FC(F)(F)C([O-])=[O:4].FC1C=CC(C2C(C[P+](CCCC)(CCCC)CCCC)=C(C(C)C)N=C(N(C)S(C)(=O)=O)N=2)=CC=1.C[Si](C)(C)N[Si](C)(C)C.[Na].[Si:54]([O:61][C@H:62]1[CH2:67][C:66](=[O:68])[O:65][C@H:64]([CH:69]=[O:70])[CH2:63]1)([C:57]([CH3:60])([CH3:59])[CH3:58])([CH3:56])[CH3:55]>C1(C)C=CC=CC=1>[Si:54]([O:61][C@@H:62]1[CH2:63][C@@H:64]([CH:69]([OH:4])[OH:70])[O:65][C:66](=[O:68])[CH2:67]1)([C:57]([CH3:60])([CH3:59])[CH3:58])([CH3:56])[CH3:55]

Participants

5

Reactant 3

HCID 16113282(2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxo-tetrahydro-2H-pyran-2-carbaldehydeHCID 45051731Sodium hexamethyidisilazaneHCID 49783151((4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)methyl)tributylphosphonium 2,2,2-trifluoro-acetate

Product 1

HCID 44128178(4R,6S)-4-(tert-butyldimethylsilyloxy)-6-(dihydroxymethyl)-tetrahydropyran-2-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent4×

Procedure

To a stirred suspension of ((4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethyl-sulfonamido)pyrimidin-5-yl)methyl)tributylphosphonium 2,2,2-trifluoro-acetate (VI′) (504 mg, 0.77 mmol) at room temperature in dry toluene (8 mL), sodium hexamethyldisilazane in toluene (1.3 mL of 0.6 M, 0.77 mmol) is added portionwise in 10 minutes. The reaction mixture is stirred for 60 min and treated at room temperature with a solution of (2S,4R)-4-(tert-butyldimethylsilyl oxy)-6-oxo-tetrahydro-2H-pyran-2-carbaldehyde (IV′) (200 mg, 0.77 mmol) in 25 mL of dry toluene obtained by dissolution of (4R,6S)-4-(tert-butyldimethylsilyloxy)-6-(dihydroxymethyl)-tetrahydropyran-2-one (V′) (214 mg, 0.77 mmol) in toluene and removal of released water. After 24 hours of stirring at room temperature the solution is treated with saturated ammonium chloride solution or water. The aqueous phase is extracted with tBuMeO (2×20 mL), and the combined organic layers dried and concentrated. The residue is purified by silica gel chromatography (elution with tBuMeO/hexane mixture) to give 273 mg (61%) of N-(5-((E)-2-((2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxo-tetrahydro-2H-pyran-2-yl)vinyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide as a white solid.

Sources & evidence

ORD record
ord-a75500f169b2450e8d7a781a027ce000
Source dataset
uspto-grants-2012_05
Patent number
US08183397B2

Reaction notes

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