2-Methylsulfanylpyrimidine-4-carbaldehyde → (5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6R)-2,6-dimethylmorpholino)-2,3-difluorophenyl)(2-(methylthio)pyrimidin-4-yl)methanol

HRID 245393Notes

Reaction equation

HRID 245393 reaction equation
[Si:1]([O:18][CH2:19][C:20]1[C:25]([N:26]2[CH2:31][C@@H:30]([CH3:32])[O:29][C@H:28]([CH3:33])[CH2:27]2)=[C:24]([F:34])[C:23]([F:35])=[CH:22][CH:21]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]C(CC)C.[CH3:41][S:42][C:43]1[N:48]=[C:47]([CH:49]=[O:50])[CH:46]=[CH:45][N:44]=1>C(OC)(C)(C)C>[Si:1]([O:18][CH2:19][C:20]1[C:25]([N:26]2[CH2:31][C@@H:30]([CH3:32])[O:29][C@H:28]([CH3:33])[CH2:27]2)=[C:24]([F:34])[C:23]([F:35])=[C:22]([CH:49]([C:47]2[CH:46]=[CH:45][N:44]=[C:43]([S:42][CH3:41])[N:48]=2)[OH:50])[CH:21]=1)([C:14]([CH3:16])([CH3:17])[CH3:15])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 154070082-Methylsulfanylpyrimidine-4-carbaldehydeHCID 67358084(2R,6R)-4-(6-((tert-butyldiphenylsilyloxy)methyl)-2,3-difluorophenyl)-2,6-dimethylmorpholine2×HCID 178418400CID 53628100

Product 1

HCID 86658062(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6R)-2,6-dimethylmorpholino)-2,3-difluorophenyl)(2-(methylthio)pyrimidin-4-yl)methanolYield 34.5%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent2×

Procedure

Starting materials: (2R,6R)-4-(6-((tert-butyldiphenylsilyloxy)methyl)-2,3-difluorophenyl)-2,6-dimethylmorpholine (Intermediate 43, 7.36 g, 14.84 mmol) in t-BuOMe (20 mL) was added s-BuLi (12.45 mL, 16.19 mmol) at −75° C. under nitrogen atmosphere. After stirring for 20 minutes at this temperature, it was then transferred via cannula to a solution of 2-(methylthio)pyrimidine-4-carbaldehyde (2.08 g, 13.49 mmol) in t-BuOMe (20 mL) (precooled down to −70° C.), the mixture was then stirred for 0.5 hour at −70° C., quenched with saturated aqueouse ammonium chloride solution and extracted with ethylacetate, dried and concentrated, purified by flash column chromatography on silica gel with Hex/EtOAc to give the desired product (3.024 g).

Workup

  1. customprecooled down to −70° C.
  2. stirringwas then stirred for 0.5 hour at −70° C.
  3. customquenched with saturated aqueouse ammonium chloride solution
  4. extractionextracted with ethylacetate
  5. customdried
  6. concentrationconcentrated
  7. custompurified by flash column chromatography on silica gel with Hex/EtOAc

Sources & evidence

ORD record
ord-5ce206498f3c4228893cf458cc05bcb4
Source dataset
uspto-grants-2014_02
Patent number
US08658641B2

Reaction notes

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