Formaldehyde → HCID 131735236, compound

HRID 626955Notes

Reaction equation

HRID 626955 reaction equation
[N:1]1([C:12](OC(C)(C)C)=O)[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C=O.[C:31](=[O:34])([O-])[O-].[Na+].[Na+].ClC1[N:43]=[CH:42][C:41]([B:44]([OH:46])[OH:45])=[CH:40][N:39]=1>C1COCC1.C(O)C>[CH2:10]([O:9][C:7]([C:4]1([CH2:31][OH:34])[CH2:3][CH2:2][N:1]([C:12]2[N:43]=[CH:42][C:41]([B:44]([OH:46])[OH:45])=[CH:40][N:39]=2)[CH2:6][CH2:5]1)=[O:8])[CH3:11]

Participants

8

Reactant 5

HCID 712FormaldehydeHCID 10340Sodium CarbonateHCID 2733832Lithium HexamethyldisilazideHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylateHCID 21747362(2-Chloropyrimidin-5-yl)boronic acid

Product 1

HCID 131735236HCID 131735236, compoundYield 83.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate (1 g, 3.89 mmol) in THF (5 mL) was stirred at −78° C. and lithium bis(trimethylsilyl)amide (1M in toluene, 5.8 mL, 29 mmol) was added dropwise, then stirred for 1 h. Paraformaldehyde (0.7370 g, 7.773 mmol) was added and the mixture was stirred for 16 h, allowing the temperature to rise slowly to ambient. The reaction mixture was quenched using saturated aqueous ammonium chloride solution, then partitioned between EtOAc and brine. The aqueous layer was further extracted using EtOAc. The combined organic extracts were dried (MgSO4) and the solvent was removed under vacuum. The resulting material was dissolved and stirred for 1 h in TFA (10 mL), then rotary evaporated to dryness. The crude residue (theoretical 0.7 g, 3.891 mmol) was dissolved in ethanol (12 mL), then sodium carbonate (1.03 g, 9.72 mmol) and (2-chloropyrimidin-5-yl)boronic acid (0.68 g, 4.3 mmol) were added and the reaction mixture was stirred at 60° C. for 2 h. LC/MS showed completion of reaction. The mixture was cooled to ambient temperature and filtered through celite. The solvent was removed to give the crude title compound (1 g, 83%) as a cream solid, which was used without further purification. LCMS (pH 10) MH+ 310, RT 0.95 minutes.

Workup

  1. stirringthe mixture was stirred for 16 h
  2. customThe reaction mixture was quenched
  3. custompartitioned between EtOAc and brine
  4. extractionThe aqueous layer was further extracted
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. customthe solvent was removed under vacuum
  7. dissolutionThe resulting material was dissolved
  8. stirringstirred for 1 h in TFA (10 mL)
  9. customrotary evaporated to dryness
  10. stirringthe reaction mixture was stirred at 60° C. for 2 h
  11. customcompletion of reaction
  12. filtrationfiltered through celite
  13. customThe solvent was removed

Sources & evidence

ORD record
ord-368dad607408430bbb2f2cbf527223f3
Source dataset
uspto-grants-2016_04
Patent number
US09309243B2

Reaction notes

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