Carbon tetrabromide → N-[(4R,4aR,6R,8aS)-6-(bromomethyl)-8a-(2,4-difluorophenyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 1775739ノート

反応式

HRID 1775739 の反応式
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:18][O:17][C@@H:16]([CH2:19]O)[CH2:15][C@H:14]1[C@@H:13]([CH3:21])[S:12][C:11]([NH:22][C:23](=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[N:10]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:51]>ClCCl>[Br:51][CH2:19][C@@H:16]1[O:17][CH2:18][C@:9]2([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])[N:10]=[C:11]([NH:22][C:23](=[O:30])[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[S:12][C@H:13]([CH3:21])[C@@H:14]2[CH2:15]1

参加物

5

反応物 3

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 89889267N-[(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(hydroxymethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

生成物 1

HCID 90089494N-[(4R,4aR,6R,8aS)-6-(bromomethyl)-8a-(2,4-difluorophenyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A solution of N-[(4R,4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(hydroxymethyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (P2) (150 mg, 0.347 mmol) in dichloromethane (7.5 mL) was cooled to 0° C. Triphenylphosphine (182 mg, 0.694 mmol) was added, followed by carbon tetrabromide (70 μL, 0.69 mmol), and the reaction mixture was removed from the ice bath and stirred for 18 hours. After addition of saturated aqueous sodium chloride solution (15 mL), the mixture was extracted with dichloromethane (2×20 mL); the combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel chromatography (Gradient: 0% to 70% ethyl acetate in heptane) provided the product as a white solid. Yield: 77.9 mg, 157 μmol, 45%. 1H NMR (400 MHz, CDCl3) δ 8.15-8.27 (br m, 2H), 7.34-7.57 (m, 4H), 6.84-6.98 (m, 2H), 4.19 (br d, J=12 Hz, 1H), 3.82-3.92 (m, 2H), 3.45-3.52 (m, 1H), 3.39 (dd, J=10.5, 5.8 Hz, 1H), 3.23-3.33 (br m, 1H), 2.89-2.98 (m, 1H), 1.93-2.02 (m, 1H), 1.6-1.73 (m, 1H), 1.28 (d, J=7 Hz, 3H).

後処理

  1. customthe reaction mixture was removed from the ice bath
  2. additionAfter addition of saturated aqueous sodium chloride solution (15 mL)
  3. extractionthe mixture was extracted with dichloromethane (2×20 mL)
  4. dry with materialthe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-36933758b8284521a04a96a6beab9641
出典データセット
uspto-grants-2016_02
特許番号
US09260455B2

反応ノート

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