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

HRID 2185739Notes

Reaction equation

HRID 2185739 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@@H:11]2[CH2:14][CH2:13][N:12]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:5]=[N:6][C:7]=1[CH3:8].[CH:22]([Sn](CCCC)(CCCC)CCCC)=[CH2:23]>C1(C)C=CC=CC=1.C1(P([Pd-4](P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:8][C:7]1[N:6]=[CH:5][C:4]([O:9][CH2:10][C@@H:11]2[CH2:14][CH2:13][N:12]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:3][C:2]=1[CH:22]=[CH2:23]

Participants

5

Reactant 2

HCID 81998TributylvinyltinHCID 229618173-(1-BOC-2-(S)-azetidinylmethoxy)-5-bromo-6-methyl-pyridine

Product 1

HCID 229618196-Methyl-5-vinyl-3-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)pyridineYield 60%

Reagents, catalysts & solvents 2

HCID 178420553HCID 178420553, compoundCatalystHCID 1140TolueneSolvent

Procedure

5-Bromo-6-methyl-3-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)pyridine (0.95 g, 2.7 mmol, Step 34a above) was treated with vinyl tributyltin (1.62 mL, 5.56 mmol) and tetrakis(triphenylphosphino)palladium(0) (0.29 g, 0.25 mmol) in toluene (30 mL) at 90° C. overnight. The reaction was cooled to ambient temperature and chromatographed on silica gel with 2:1 hexane-EtOAc eluent to provide 6-methyl-5-vinyl-3-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)pyridine (0.49 g, 60%): MS (CI/NH3) m/z: 305 (M+H)+; 1H NMR (300 MHz, CDCl3) δ1.42 (s, 9H), 2.22-2.38 (m, 2H), 2.52 (s, 3H), 3.91 (dt, J=2, 6 Hz, 2H), 4.13 (dd, J=3, 10 Hz, 1H), 4.30-4.36 (m, 1H), 4.49-4.55 (m, 1H), 5.40 (dd, J=1, 11 Hz, 1H), 5.64 (dd, J=1, 17 Hz, 1H), 6.84 (dd, J=11, 17 Hz, 1H), 7.32 (d, J=3 Hz, 1), 8.13 (d, J=3 Hz, 1H). The product from above (0.47 g,1.53 mmol) was treated with 8 mL of 1:1 TFA-methylene chloride at 0° C. for 2 hours. The volatile components were evaporated in vacuo, and the residue was diluted with saturated aqueous sodium bicarbonate and extracted with CH2Cl2. The combined organic layers were washed with water and dried over MgSO4 to provide the product (277 mg, 89% yield). Half of the sample was dissolved in ether and treated with 1 M HCl in ether to provide 85 mg of the title compound as an off-white solid: mp 154-155° C.; [α]D −8.9 (c 0.45, MeOH); 1H NMR (CD3OD) δ2.63-2.77 (m, 2H), 2.74 (s, 3H), 4.08-4.16 (m, 2H), 4.52-4.64 (m, 2H), 4.85-4.95 (m, 1H), 5.80 (d, J=11 Hz, 1H), 6.15 (d, J=17 Hz, 1H), 7.02 (dd, J=11, 17 Hz, 1H), 8.36 (d, J=2 Hz), 1H, 8.48 (d, J=2 Hz, 1H); MS (CI/NH3) m/z; 205 (M+H)+; Anal. Calcd for C12H16N2O.2.1 HCl: C, 51.32; H, 6.50; N, 9.97. Found: C, 51.60; H, 6.21; N, 9.82.

Workup

  1. customchromatographed on silica gel with 2:1 hexane-EtOAc eluent

Sources & evidence

ORD record
ord-07345b5594a0409eaea495fb5aabbf5f
Source dataset
uspto-grants-2002_06
Patent number
US06403575B1

Reaction notes

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