Methanol → tert-butyl 3-(fluoromethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate

HRID 1692985Notes

Reaction equation

HRID 1692985 reaction equation
[F:1][CH:2](S(C1C=CC=CC=1)(=O)=O)[C:3]1([N:14]2[CH:18]=[C:17]([C:19]3[C:20]4[CH:27]=[CH:26][N:25]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:21]=4[N:22]=[CH:23][N:24]=3)[CH:16]=[N:15]2)[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1.P([O-])([O-])(O)=O.[Na+].[Na+].CO>CCOC(C)=O.[Na].[Hg]>[F:1][CH2:2][C:3]1([N:14]2[CH:18]=[C:17]([C:19]3[C:20]4[CH:27]=[CH:26][N:25]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:33])[CH3:34])[C:21]=4[N:22]=[CH:23][N:24]=3)[CH:16]=[N:15]2)[CH2:4][N:5]([C:7]([O:9][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:8])[CH2:6]1

Participants

6

Reactant 3

HCID 887MethanolHCID 24203Sodium Phosphate, DibasicHCID 66824410tert-butyl 3-[fluoro(phenylsulfonyl)methyl]-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate

Product 1

HCID 66824231tert-butyl 3-(fluoromethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylateYield 49.2%

Reagents, catalysts & solvents 2

HCID 9837419Sodium amalgamCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

To a mixture of tert-butyl 3-[fluoro(phenylsulfonyl)methyl]-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate (0.312 g, 0.485 mmol) and disodium hydrogen phosphate (1.38 g, 9.71 mmol) in methanol (7.5 mL, 180 mmol) was added sodium mercury amalgam (2.17 g, 9.71 mmol), under nitrogen, at −20° C. The reaction was stirred at −20 to 0° C. for 1 h, diluted with EtOAc, then quenched with sat. ammonium chloride. The mixture was filtered through Celite and the solid collected was treated with elemental sulfur powder to destroy the mercury residue. The filtrate layers were separated and the organic layers were washed with brine, dried over sodium sulfate and evaporated. The residue was purified on silica gel, eluting with 0 to 80% EtOAc in hexane, to give the desired product (120 mg, 49.2%). LCMS calculated for C24H36FN6O3Si(M+H)+: m/z=503.3; Found: 503.2.

Workup

  1. customat −20° C
  2. customquenched with sat. ammonium chloride
  3. filtrationThe mixture was filtered through Celite
  4. customthe solid collected
  5. additionwas treated with elemental sulfur powder
  6. customto destroy the mercury residue
  7. customThe filtrate layers were separated
  8. washthe organic layers were washed with brine
  9. dry with materialdried over sodium sulfate
  10. customevaporated
  11. customThe residue was purified on silica gel
  12. washeluting with 0 to 80% EtOAc in hexane

Sources & evidence

ORD record
ord-fe86a5428f28423e815a3fa5e807424d
Source dataset
uspto-grants-2012_04
Patent number
US08158616B2

Reaction notes

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