Sodium hydride → N-((S)-7-fluoro-2,2-dimethyl-6-neopentyl-3,4-dihydro-2H-pyrano[2,3-b]pyridin-4-yl)-2-methylpropane-2-sulfinamide

HRID 1009136Notes

Reaction equation

HRID 1009136 reaction equation
[Si]([O:8][C:9]1([CH2:13][C@H:14]([NH:28][S:29]([C:31]([CH3:34])([CH3:33])[CH3:32])=[O:30])[C:15]2[C:16](F)=[N:17][C:18]([F:26])=[C:19]([CH2:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH:20]=2)[CH2:12]C[CH2:10]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].[H-].[Na+]>C1COCC1>[F:26][C:18]1[N:17]=[C:16]2[O:8][C:9]([CH3:12])([CH3:10])[CH2:13][C@H:14]([NH:28][S:29]([C:31]([CH3:34])([CH3:33])[CH3:32])=[O:30])[C:15]2=[CH:20][C:19]=1[CH2:21][C:22]([CH3:25])([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2724141Tetrabutylammonium FluorideHCID 67305123N-((S)-2-(1-(tert-butyldimethylsilyloxy)cyclobutyl)-1-(2,6-difluoro-5-neopentylpyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide

Product 1

HCID 67304513N-((S)-7-fluoro-2,2-dimethyl-6-neopentyl-3,4-dihydro-2H-pyrano[2,3-b]pyridin-4-yl)-2-methylpropane-2-sulfinamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a 150 mL RBF was added N—((S)-2-(1-(tert-butyldimethylsilyloxy)cyclobutyl)-1-(2,6-difluoro-5-neopentylpyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide (0.070 g, 0.14 mmol), THF (3 mL), and TBAF, 1M in THF (0.14 ml, 0.14 mmol). The reaction was stirred at RT. After 20 minutes, the reaction was eluted through a plug of silica gel with THF. The resulting filtrate was concentrated in vacuo and taken up in THF (20 mL) and treated with NaH (0.035 g, 0.88 mmol, 60% in mineral oil). The reaction was stirred at 40° C. for 16 hours. The reaction was allowed to cool to RT and quenched with sat'd NH4Cl, and extracted with EtOAc (25 mL). The combined organic layers were concentrated in vacuo to give N—((S)-7-fluoro-2,2-dimethyl-6-neopentyl-3,4-dihydro-2H-pyrano[2,3-b]pyridin-4-yl)-2-methylpropane-2-sulfinamide. This material was carried forward without further purification. MS m/z: 383 (M+1).

Workup

  1. washthe reaction was eluted through a plug of silica gel with THF
  2. concentrationThe resulting filtrate was concentrated in vacuo
  3. stirringThe reaction was stirred at 40° C. for 16 hours
  4. temperatureto cool to RT
  5. customquenched with sat'd NH4Cl
  6. extractionextracted with EtOAc (25 mL)
  7. concentrationThe combined organic layers were concentrated in vacuo

Sources & evidence

ORD record
ord-652927d418ad4fc7bbc3f8eb7abd8e75
Source dataset
uspto-grants-2011_07
Patent number
US07973047B2

Reaction notes

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