Pyridine → HCID 59464264, compound

HRID 1713822Notes

Reaction equation

HRID 1713822 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[N:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.N1C=CC=CC=1.Cl[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>C1COCC1>[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[N:16]=[CH:15][C:14]([NH:17][C:25](=[O:26])[O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:13][CH:12]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 10387Benzyl chloroformate2×HCID 59464242HCID 59464242, compound

Product 1

HCID 59464264HCID 59464264, compoundYield 102%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To an ice water cooled solution of 6-(1,4-dioxaspiro[4.5]dec-8-yl)pyridin-3-amine (3.08 g, 13.15 mmol), prepared as above, in THF (50 mL) was added pyridine (3.19 mL, 39.44 mmol) followed by benzyl chloroformate (1.9 mL, 13.15 mmol). The resulting suspension was allowed to stir at 0° C., then after 2 hrs a further 0.5 mL of benzyl chloroformate was added and reaction mixture was allowed to stir at ambient temperature overnight. It was partitioned between EtOAc (100 mL) and water (50 mL), the organic phase was separated and the aqueous phase re extracted into EtOAc (200 mL). The organic extracts were combined, dried and concentrated to leave crude product. This was purified on a 120 g silica SiliCycle cartridge, eluting with 30-50% EtOAc/isohexane using an Isco Companion, to provide the title compound (4.94 g, 100%); 1H NMR (CDCl3) δ 1.66-1.97 (m, 8H), 2.70-2.77 (m, 1H), 3.97 (s, 4H), 5.21 (s, 2H), 6.71 (s, 1H), 7.16 (d, 1H), 7.35-7.41 (m, 5H), 7.91 (s, 1H), 8.37 (s, 1H); MS m/e MH+ 369.

Workup

  1. customreaction mixture
  2. stirringto stir at ambient temperature overnight
  3. customIt was partitioned between EtOAc (100 mL) and water (50 mL)
  4. customthe organic phase was separated
  5. extractionthe aqueous phase re extracted into EtOAc (200 mL)
  6. customdried
  7. concentrationconcentrated
  8. customto leave crude product
  9. customThis was purified on a 120 g silica SiliCycle cartridge
  10. washeluting with 30-50% EtOAc/isohexane using an Isco Companion

Sources & evidence

ORD record
ord-4ae10adbbd734bc5814005a8983240c2
Source dataset
uspto-grants-2010_09
Patent number
US07795283B2

Reaction notes

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