Methanol → (2S,3R)-Isopropyl 3-(allyloxy)-2-((6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridin-2-yl)methyl)-4-oxobutanoate

HRID 73485

反応式

HRID 73485 の反応式
[CH2:1]([O:4][C@H:5]([C@H:12]([CH2:19][C:20]1[CH:25]=[C:24]([CH3:26])[CH:23]=[C:22]([N:27]2[C:31]([CH3:32])=[CH:30][CH:29]=[C:28]2[CH3:33])[N:21]=1)[C:13]([O:15][CH:16]([CH3:18])[CH3:17])=[O:14])[C:6](OC(C)C)=[O:7])[CH:2]=[CH2:3].CC(C[Al]CC(C)C)C.CO.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C1(C)C=CC=CC=1>[CH2:1]([O:4][C@@H:5]([CH:6]=[O:7])[C@H:12]([CH2:19][C:20]1[CH:25]=[C:24]([CH3:26])[CH:23]=[C:22]([N:27]2[C:31]([CH3:32])=[CH:30][CH:29]=[C:28]2[CH3:33])[N:21]=1)[C:13]([O:15][CH:16]([CH3:18])[CH3:17])=[O:14])[CH:2]=[CH2:3]

参加物

6

反応物 4

HCID 887MethanolHCID 9855836Potassium sodium tartarateHCID 16682954DibahHCID 89419083(2R,3S)-Diisopropyl 2-(allyloxy)-3-((6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridin-2-yl)methyl)succinate

生成物 1

HCID 44543305(2S,3R)-Isopropyl 3-(allyloxy)-2-((6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridin-2-yl)methyl)-4-oxobutanoate収率 62%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
-78 °C

実験手順

To a solution of diisopropyl ester 10 (140 mg, 0.31 mmol) in toluene (5 mL) at −78° C. was added dropwise a solution of Dibal-H (1.0 M in toluene, 620 μL, 0.62 mmol) along the side of the flask over a period of 15 min. The reaction was maintained at −78° C. during the addition and allowed to react at the same temperature for 7 h. To the resulting solution at −78° C., MeOH (100 μL) was added dropwise along the side of the flask to quench the reaction. The reaction mixture was warmed to −20° C. and poured directly onto a vigorously stirring Rochelle's solution (potassium sodium tartrate solution, 5 mL). The viscous solution was allowed to stir for an additional 30 min then settled down to two clear phases. The organic layer was separated, and the aqueous layer was extracted with ether (3×5 mL). The combined organic layers were dried over Na2SO4 and concentrated. The crude product was purified by flash column chromatography (EtOAc/hexanes, 1:9-1:4) to give 16 (75 mg, 0.19 mmol, 62%) as a colorless oil: 1H NMR (500 MHz, CDCl3) δ 1.11-1.13 (d, J=6.0, 3H), 1.16-1.18 (d, J=6.5, 3H), 2.11 (s, 6H), 2.40 (s, 3H), 3.01-3.04 (dd, J=6.5, 14.5 Hz, 1H), 3.28-3.33 (dd, J=8.0, 15.0 Hz, 1H), 3.60-3.73 (ddd, J=4.0, 7.0, 11.5 Hz, 1H), 3.85-3.86 (dd, J=1.0, 4.5 Hz, 1H), 4.03-4.06 (dd, J=6.0, 13.0 Hz, 1H), 4.21-4.25 (dd, J=6.0, 12.5 Hz, 1H), 4.96-4.98 (m, 1H), 5.19-5.22 (dd, J=1.5, 10.5 Hz, 1H), 5.24-5.28 (dd, J=2.0, 17.5 Hz, 1H), 5.86-5.91 (m, 3H), 6.88 (s, 1H), 7.03 (s, 1H), 9.75-9.77 (d, J=1.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 13.5, 21.2, 22.0, 35.4, 46.8, 69.1, 72.7, 83.1, 106.9, 107.0, 118.6, 120.7, 123.7, 128.7, 133.9, 149.9, 151.9, 158.5, 171.0, 202.5; LCQ-MS (M+H+) calcd for C23H31N2O4 399. found 399; LC-TOF-MS (M+H+) calcd for C23H31N2O4 399.22838. found 399.22859.

後処理

  1. customto react at the same temperature for 7 h
  2. customto quench
  3. customthe reaction
  4. temperatureThe reaction mixture was warmed to −20° C.
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ether (3×5 mL)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. concentrationconcentrated
  9. customThe crude product was purified by flash column chromatography (EtOAc/hexanes, 1:9-1:4)

出典と根拠

ORDレコード
ord-c29b9f16588b4479bff1346d398d2e5c
出典データセット
uspto-grants-2014_09
特許番号
US08829187B1

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