Sodium hydride → HCID 86706458, compound

HRID 919589Notes

Reaction equation

HRID 919589 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[H-].[Na+].Cl[C:18]1[C:19]2[CH:26]=[CH:25][N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:20]=2[N:21]=[CH:22][N:23]=1>CS(C)=O.O>[CH3:32][Si:31]([CH3:34])([CH3:33])[CH2:30][CH2:29][O:28][CH2:27][N:24]1[C:20]2[N:21]=[CH:22][N:23]=[C:18]([O:1][C@H:2]3[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]3)[C:19]=2[CH:26]=[CH:25]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 1514399tert-butyl (3S)-3-hydroxypiperidine-1-carboxylateHCID 467367974-Chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo(2,3-d)pyrimidine

Product 1

HCID 86706458HCID 86706458, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Procedure

To a solution of (S)-tert-butyl 3-hydroxypiperidine-1-carboxylate (0.4 g, 2.0 mmol) in DMSO (5 mL) under nitrogen, was added NaH (60% suspension in mineral oil, 79 mg, 2.0 mmol). After the reaction was stirred for 1.5 h at rt, a solution of 4-chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (564 mg, 2.0 mmol) in DMSO (5 mL) was added dropwise at rt and the mixture was heated at 50° C. for 2 h. The reaction mixture was cooled to rt, diluted with water (10 mL) and extracted with EtOAc (4×60 mL). The combined organic layer was washed with water (50 mL), dried over Na2SO4 and concentrated in vacuo to give the crude compound which was purified by column chromatography (silica gel, gradient EtOAc in Hexanes) to give (750 mg, 85%) of the titled intermediate.

Workup

  1. temperaturethe mixture was heated at 50° C. for 2 h
  2. temperatureThe reaction mixture was cooled to rt
  3. extractionextracted with EtOAc (4×60 mL)
  4. washThe combined organic layer was washed with water (50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customto give the crude compound which
  8. customwas purified by column chromatography (silica gel, gradient EtOAc in Hexanes)

Sources & evidence

ORD record
ord-6aee8b4855f846bdabf570df3b94569a
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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