Toluene → HCID 59731886, compound

HRID 132350Notes

Reaction equation

HRID 132350 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[CH:15]([C:17]1[C:18]([NH:23][C:24](=O)[O:25]CC)=[N:19][CH:20]=[CH:21][CH:22]=1)=O.[BH4-].[Na+].C1(C)C=CC=CC=1>CO.C(O)(=O)C>[O:25]=[C:24]1[NH:23][C:18]2[N:19]=[CH:20][CH:21]=[CH:22][C:17]=2[CH2:15][N:1]1[CH:2]1[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 12682914-Amino-1-Boc-piperidineHCID 4311764Sodium borohydrideHCID 59731971HCID 59731971, compound

Product 1

HCID 59731886HCID 59731886, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×

Conditions

Temperature
60 °C

Procedure

4-Amino-1-N-Boc-piperidine (290 mg, 1.4 mmol) was added to a solution of ethyl 3-formylpyridin-2-ylcarbamate (240 mg, 1.2 mmol) in methanol (10 mL). Mixture was warmed to 60° C. and held for 1.5 hours. Mixture was cooled to room temperature. Sodium borohydride (62 mg, 1.6 mmol) was added to the mixture. Reaction stirred at room temperature for 30 minutes. Toluene (20 mL) was added to the mixture followed by acetic acid (1.0 mL). Mixture was warmed to 110° C. Methanol was driven from the reaction mixture and collected in a Dean-Stark trap. Mixture was held at 110° C. for 5 hours. Mixture was cooled to room temperature and held for 16 hours. Reaction was quenched with aqueous sodium bicarbonate. Mixture was extracted with ethyl acetate (2×30 mL). Combined organics were washed successively with water (30 mL) and brine (20 mL). Organic layer was dried (magnesium sulfate), filtered and concentrated in vacuo. Silica gel chromatography afforded the title compound as white solid in 44% yield. MS m/e (M−H)−=311.2.

Workup

  1. temperatureMixture was cooled to room temperature
  2. customReaction
  3. temperatureMixture was warmed to 110° C
  4. customcollected in a Dean-Stark trap
  5. waitMixture was held at 110° C. for 5 hours
  6. temperatureMixture was cooled to room temperature
  7. waitheld for 16 hours
  8. customReaction
  9. customwas quenched with aqueous sodium bicarbonate
  10. extractionMixture was extracted with ethyl acetate (2×30 mL)
  11. washCombined organics were washed successively with water (30 mL) and brine (20 mL)
  12. dry with materialOrganic layer was dried (magnesium sulfate)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-32bfb3b2bce4414e8726b2d9e1bffb13
Source dataset
uspto-grants-2008_06
Patent number
US07384931B2

Reaction notes

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