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Ammonium Chloride → (8R, 9R)-8-(t-Butydimethylsilyloxy)-6-methoxymethyl-2,3-dimethyl-9-phenyl-5,6,7,8,9,10-hexahydroimidazo[1,2-h][1,7]naphthyridin-7-one

HRID 2121485
ノート
印刷プレビュー

反応式

HRID 2121485 の反応式
[CH3:1][O:2][CH2:3][CH:4]1[CH2:9][N:8]2[C:10]([CH3:14])=[C:11]([CH3:13])[N:12]=[C:7]2[C:6](=O)[CH2:5]1.[NH2:16][C@H:17]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C@@H:18]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[C:19](OCC)=[O:20].C([N-]C(C)C)(C)C.[Li+].[Cl-].[NH4+]>C1(C)C=CC(S(O)(=O)=O)=CC=1.O1CCCC1.C1(C)C=CC=CC=1.O>[Si:25]([O:24][C@H:18]1[C:19](=[O:20])[C:5]2[CH:4]([CH2:3][O:2][CH3:1])[CH2:9][N:8]3[C:10]([CH3:14])=[C:11]([CH3:13])[N:12]=[C:7]3[C:6]=2[NH:16][C@@H:17]1[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 4

HCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 218739786-Methoxymethyl-2,3-dimethyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-oneHCID 69232107ethyl (2R,3R)-3-amino-2-(t-butyldimethylsilanyloxy)-3-phenylpropionate

生成物 1

HCID 131724351(8R, 9R)-8-(t-Butydimethylsilyloxy)-6-methoxymethyl-2,3-dimethyl-9-phenyl-5,6,7,8,9,10-hexahydroimidazo[1,2-h][1,7]naphthyridin-7-one
収率 87.1%

試薬・触媒・溶媒 4

HCID 6101p-Toluenesulfonic acid触媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-25 °C

実験手順

By using a water separator, a mixture of 2.66 g of 6-methoxymethyl-2,3-dimethyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-one, 4.27 g of ethyl (2R, 3R)-3-amino-2-(t-butyldimethylsilyloxy)-3-phenylpropionate, 70 mg of p-toluenesulfonic acid and 15 ml of toluene is boiled at reflux for 1.5 h. After cooling, 15 ml of tetrahydrofuran are added. With introduction of argon, the mixture is cooled to an internal temperature of −25° C. 15.4 ml of a commercial 2 molar solution of lithium diisopropylamide (Aldrich) are then added. The solution is stirred at −25° C. for 30 min. The solution is then allowed to warm to room temperature (30 min.) and poured into 30 ml of saturated aqueous ammonium chloride solution, the mixture is extracted three times with in each case 20 ml of ethyl acetate and the combined extracts are concentrated to dryness in vacuo. Purification on silica gel (mobile phase: methylene chloride/methanol=100/3) gives 5.2 g of the title compound as a yellowish amorphous solid. 1H-NMR(CDCl3, δ), 7.33-7.45 (m, 5H), 5.95 (d, 1H), 4.55-4.65 (dd, 1H), 4.2-4.4 (dd, 2H), 3.2-3.75 (m, 3H), 3.3 (s, 3H), 2.91-3.1 (q, 1H), 2.15 (s, 6H), 0.6 (d, 9H), 0.08 (d, 3H), −0.3 (d, 3H).

後処理

  1. temperatureat reflux for 1.5 h
  2. temperatureAfter cooling
  3. temperatureto warm to room temperature (30 min.)
  4. extractionthe mixture is extracted three times with in each case 20 ml of ethyl acetate
  5. concentrationthe combined extracts are concentrated to dryness in vacuo
  6. customPurification on silica gel (mobile phase: methylene chloride/methanol=100/3)

出典と根拠

ORDレコード
ord-275316072a90456482196e31998af6f4
出典データセット
uspto-grants-2004_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06696461B2

反応ノート

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