Formaldehyde → (3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-((S)-1-phenyl-propyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid methyl ester

HRID 391782ノート

反応式

HRID 391782 の反応式
[CH3:1][O:2][C:3](=[O:42])[C@@H:4]([NH:32][C@H:33]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH2:34][CH3:35])[CH2:5][C:6]1[CH:31]=[CH:30][C:9]2[O:10][C@@H:11]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=4)=[CH:16][CH:15]=3)[CH2:12][O:13][C:8]=2[CH:7]=1.C=O.F[C:46](F)(F)C(O)=O.C([O-])(O)=O.[Na+]>O1CCOCC1>[CH3:1][O:2][C:3]([C@@H:4]1[CH2:5][C:6]2[CH:7]=[C:8]3[O:13][CH2:12][C@H:11]([C:14]4[CH:15]=[CH:16][C:17]([O:20][CH2:21][C:22]5[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=5)=[CH:18][CH:19]=4)[O:10][C:9]3=[CH:30][C:31]=2[CH2:46][N:32]1[C@H:33]([C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)[CH2:34][CH3:35])=[O:42]

参加物

6

反応物 4

HCID 712Formaldehyde2 回HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 58327321(S)-3-{(S)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-((S)-1-phenyl-propylamino)-propionic acid methyl ester

生成物 1

HCID 58327581(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-((S)-1-phenyl-propyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid methyl ester

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

(S)-3-{(S)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-((S)-1-phenyl-propylamino)-propionic acid methyl ester (893 mg) was dissolved in 80 mL dry dioxane and 133 mg paraformaldehyde and 20 mL trifluoroacetic acid were added. The reaction stirred 12 h at rt, then 66 mg more paraformaldehyde was added while stirring at rt. After 3 h aqueous NaHCO3 was added until a pH of 7 was achieved, then the mixture was extracted with EtOAc. The organic extract was washed with brine and dried over Na2SO4 and evaporated. The residue was purified by silica gel flash chromatography (9:1 to 8:2 hexanes/EtOAc) to give 872 mg desired product after drying. 1H NMR (400 MHz, acetone-d6): 7.72 (d, 1H), 7.62 (d, 1H), 7.51-7.43 (m, 3H), 7.38-7.25 (m, 5H), 7.10 (m, 2H), 6.67 (s, 1H), 6.60 (s, 1H), 5.20 (s, 2H), 5.09 (m, 1H), 4.30 (m, 1H), 4.13 (m, 2H), 3.99 (m, 1H), 3.92 (m, 1H), 3.59 (m, 1H), 3.52 (s, 3H), 2.96-2.78 (m, 2H), 2.16 (m, 1H), 1.68 (m, 1H), 0.65 (t, 3H).

後処理

  1. stirringwhile stirring at rt
  2. extractionthe mixture was extracted with EtOAc
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe residue was purified by silica gel flash chromatography (9:1 to 8:2 hexanes/EtOAc)

出典と根拠

ORDレコード
ord-1db92398053648cfa22e246606212ebd
出典データセット
uspto-grants-2013_02
特許番号
US08383644B2

反応ノート

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