3-Hydroxy-1,2,3,6-tetrahydropyridine, N-BOC protected → Tert-butyl 3-oxo-1,2,3,6-tetrahydropyridine-1-carboxylate

HRID 1801539Notes

Reaction equation

HRID 1801539 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[CH:11][CH:10]([OH:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[CH:11][C:10](=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 177501313-Hydroxy-1,2,3,6-tetrahydropyridine, N-BOC protectedHCID 178418287HCID 178418287, compound

Product 1

HCID 11052578Tert-butyl 3-oxo-1,2,3,6-tetrahydropyridine-1-carboxylateYield 61.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-Hydroxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (3.1 g, 17.3 mmol) was dissolved in dichloromethane (30 mL) under an argon atmosphere. Pyridinium chlorochromate (5 g, 23 mmol) was added in portions over 1 hour. The dichloromethane solution was filtered through silica gel (100 g), eluting with dichloromethane. The crude brown solid (2.84 g) was purified by MPLC (Companion) on a silica cartridge (40 g), eluting with 100% heptane followed by a gradient of ethyl acetate/heptane (0 to 60%). The product containing fractions were combined, concentrated, and dried under high vacuum for 1 hour at room temperature to provide 3-oxo-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (2.1 g, 61% yield) as a clear oil that solidified on standing at low temperature. 1H NMR (300 MHz, CDCl3/TMS): δ=6.95 (m, 1H), 6.08 (d, 1H, J=10.5 Hz), 4.15 (m, 2H), 4.02 (br s, 2H), 1.39 (s, 9H). 13C NMR (75 MHz, CDCl3/TMS): δ=193.11, 154.02, 147.17, 127.40, 80.89, 51.97, 42.69, 28.41.

Workup

  1. filtrationThe dichloromethane solution was filtered through silica gel (100 g)
  2. washeluting with dichloromethane
  3. customThe crude brown solid (2.84 g) was purified by MPLC (Companion) on a silica cartridge (40 g)
  4. washeluting with 100% heptane
  5. additionThe product containing fractions
  6. concentrationconcentrated
  7. customdried under high vacuum for 1 hour at room temperature

Sources & evidence

ORD record
ord-ef5ed74e8aa440f3978aae3951c2c98a
Source dataset
uspto-grants-2013_01
Patent number
US08349833B2

Reaction notes

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