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

HRID 367074ノート

反応式

HRID 367074 の反応式
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]

参加物

5

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178420553HCID 178420553、化合物触媒HCID 1140Toluene溶媒

実験手順

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) δ 1.42 (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, 1H), 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) δ 2.63-2.77 (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.

後処理

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

出典と根拠

ORDレコード
ord-593c335f105e4fe8906612b4d62b0fea
出典データセット
uspto-grants-2000_10
特許番号
US06133253

反応ノート

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