6-Methyl-5-vinyl-3-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)pyridine → 5-ethyl-6-methyl-3-(1-t-butyloxycarbonyl-2-(S)-azetidinylmethoxy)pyridine

HRID 367075Notes

Reaction equation

HRID 367075 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH2:9][C@@H:10]2[CH2:13][CH2:12][N:11]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:4][C:3]=1[CH:21]=[CH2:22].[H][H]>CO.[Pd]>[CH2:21]([C:3]1[CH:4]=[C:5]([O:8][CH2:9][C@@H:10]2[CH2:13][CH2:12][N:11]2[C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH:6]=[N:7][C:2]=1[CH3:1])[CH3:22]

Participants

5

Reactant 2

HCID 229618196-Methyl-5-vinyl-3-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)pyridineHCID 178418361HCID 178418361, compound

Product 1

HCID 213452065-ethyl-6-methyl-3-(1-t-butyloxycarbonyl-2-(S)-azetidinylmethoxy)pyridineYield 45.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

6-Methyl-5-vinyl-3-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)pyridine (0.26 g, 0.86 mmol, from Example 35 above) was dissolved in MeOH (15 mL) and treated with 10% Pd/C (50 mg) and 1 atm hydrogen gas. After 1 day, the catalyst was removed, the solvent evaporated, and the residue was chromatographed (silica gel; hexanes-EtOAc, 1:1) to provide 5-ethyl-6-methyl-3-(1-t-butyloxycarbonyl-2-(S)-azetidinylmethoxy)pyridine (0.12 g, 45%): MS (CI/NH3) m/z: 307 (M+H)+ ; 1H NMR (300 MHz, CDCl3) δ 1.23 (t, J=7 Hz, 3H), 1.42 (s, 9H), 2.23-2.38 (m, 2H), 2.47 (s, 3H), 2.60 (q, J=7 Hz, 2H), 3.86-3.93 (m, 2H), 4.12 (dd, J=3, 9 Hz, 1H), 4.29 (dd, J=5,10 Hz, 1H), 4.43-4.53 (m, 1H), 7.04 (d, J=3 Hz, 1H), 8.05 (d, J=3 Hz, 1H). The product from above (0.26 g, 0.85 mmol) was treated with 10 mL of 1:1 TFA-methylene chloride at 0° C. for 1 hour. The residue was diluted with saturated sodium bicarbonate and extracted into CHCl3. The organic layer was washed with water, dried over MgSO4, and evaporated to provide of the free base of the title compound (132 mg, 75%). This was dissolved in ether and treated with 1 M HCl in ether and the resulting salt collected by filtration to provide the title compound (52 mg, 25%). The mother liquor was evaporated to further provide 73 mg of the title compound: mp 150-153° C.; [α]D -7.6 (c 0.62, MeOH); 1H NMR (300 MHz, CD3OD) δ 1.34 (t, J=7 Hz, 3H), 2.63-2.76 (m, 2H), 2.72 (s, 3H), 4.04-4.19 (m, 2H), 4.49-4.63 (m, 2H), 4.88-4.97 (m, 1H), 8.14 (d, J=2 Hz, 1H), 8.40 (d, J=2 Hz); MS (CI/NH3): m/z 207 (M+H+). Anal. Calcd for C12H18N2O.2HCl.0.1 H2O: C, 51.29; H, 7.25; N, 9.97. Found: C, 51.21; H, 7.14; N, 9.77.

Workup

  1. customthe catalyst was removed
  2. customthe solvent evaporated
  3. customthe residue was chromatographed (silica gel; hexanes-EtOAc, 1:1)

Sources & evidence

ORD record
ord-0d1dd91ac7ac408d907e1480d7cf8a95
Source dataset
uspto-grants-2000_10
Patent number
US06133253

Reaction notes

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