Triethylamine → (S,S)-5-[4-(Benzothiazol-2-yloxy)-benzyl]-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 545592ノート

反応式

HRID 545592 の反応式
Cl[CH2:2][C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[S:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:5][CH:4]=1.[C:19]([O:23][C:24]([N:26]1[CH2:31][C@@H:30]2[CH2:32][C@H:27]1[CH2:28][NH:29]2)=[O:25])([CH3:22])([CH3:21])[CH3:20].C(N(CC)CC)C>CC#N>[C:19]([O:23][C:24]([N:26]1[CH2:31][C@@H:30]2[CH2:32][C@H:27]1[CH2:28][N:29]2[CH2:2][C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[S:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:5][CH:4]=1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 67207884HCID 67207884、化合物

生成物 1

HCID 67206277(S,S)-5-[4-(Benzothiazol-2-yloxy)-benzyl]-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester収率 71.1%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a stirred solution of 2-(4-chloromethyl-phenoxy)-benzothiazole (15.3 g, 55.3 mmol) and (S,S)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (13.2 g, 66.4 mmol) in CH3CN (200 mL) was added triethylamine (Et3N) (11.5 mL, 82.9 mmol). The resulting solution was stirred at rt for 24 h and then concentrated. The crude residue was then partitioned between CH2Cl2 (800 mL) and saturated (satd.) aqueous (aq.) NaHCO3 (200 mL). The organic layer was separated, dried (Na2SO4), filtered and concentrated. Purification by silica gel flash chromatography (10% to 40% ethyl acetate (EtOAc) in hexanes) afforded the title compound as a white foam (17.2 g, 71%). MS (ESI): mass calcd. for C24H27N3O3S, 437.18; m/z found, 438.2 [M+H]+. 1H NMR (500 MHz, CDCl3, mixture of rotamers): 7.73 (d, J=7.1 Hz, 1H), 7.66 (d, J=7.1 Hz, 1H), 7.42 (d, J=8.1 Hz, 2H), 7.38 (m, 1H), 7.32-7.24 (br m, 3H), 4.40 (br m, 0.5H), 4.26 (br m, 0.5H), 3.76 (br d, J=9.7 Hz, 2H), 3.63 (br d, J=10.5 Hz, 0.5H), 3.50 (br m, 1H), 3.46 (m, 0.5H), 3.18 (br m, 1H), 2.93 (br d, J=8.8 Hz, 0.5H), 2.88 (br d, J=9.4 Hz, 0.5H), 2.73 (br d, J=9.2 Hz, 0.5H), 2.55 (br d, J=9.2 Hz, 0.5H), 1.87 (br t, J=8.8 Hz, 1H), 1.74 (br d, J=9.3 Hz, 0.5H), 1.68 (br d, J=9.3 Hz, 0.5H), 1.47 (s, 9H).

後処理

  1. concentrationconcentrated
  2. customThe crude residue was then partitioned between CH2Cl2 (800 mL) and saturated (satd.) aqueous (aq.) NaHCO3 (200 mL)
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel flash chromatography (10% to 40% ethyl acetate (EtOAc) in hexanes)

出典と根拠

ORDレコード
ord-3704ae57ba384c05bbacab5a1ff708d5
出典データセット
uspto-grants-2011_05
特許番号
US07935725B2

反応ノート

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