Sodium Iodide → [(S)-1-(6-Bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-carbamic acid tert-butyl ester

HRID 1481894ノート

反応式

HRID 1481894 の反応式
[C:1]([O:5][C:6](=[O:20])[NH:7][C@@H:8]1[C:14](=[O:15])[NH:13][C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[NH:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Br:31][C:32]1[CH:33]=[C:34]2[C:39](=[CH:40][CH:41]=1)[C:38]([CH2:42]Cl)=[C:37]([O:44][CH3:45])[CH:36]=[CH:35]2.[Na+].[I-]>C1COCC1>[C:1]([O:5][C:6](=[O:20])[NH:7][C@@H:8]1[C:14](=[O:15])[N:13]([CH2:42][C:38]2[C:39]3[C:34](=[CH:33][C:32]([Br:31])=[CH:41][CH:40]=3)[CH:35]=[CH:36][C:37]=2[O:44][CH3:45])[C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[NH:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

参加物

6

反応物 4

HCID 5238Sodium IodideHCID 7371226-Bromo-1-(chloromethyl)-2-methoxynaphthaleneHCID 2733832Lithium HexamethyldisilazideHCID 22881971tert-butyl N-[(3S)-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]carbamate2 回

生成物 1

HCID 72713836[(S)-1-(6-Bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-carbamic acid tert-butyl ester収率 72.8%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of ((S)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl)-carbamic acid tert-butyl ester (Intermediate 2) (6.5 g, 23.48 mmol) in THF (100 mL) at −78° C. was added 1 M LiHMDS (4.7 g, 28 mL, 28 mmol). The cooling bath was removed and the mixture stirred at RT for 1 h. The mixture was cooled to −78° C. and a mixture of 6-bromo-1-chloromethyl-2-methoxy-naphthalene (8.0 g, 28.12 mmol) and NaI (4.2 g, 28.12 mmol) in dry THF (30 mL) was added dropwise. The cooling bath was removed and the mixture stirred at RT for 18 h. The mixture was diluted with saturated NH4Cl, extracted with ethyl acetate and the organic layer washed with water, brine, dried (Na2SO4) and concentrated to give a material which was purified by silica gel chromatography to afford the title compound (9 g, 72%) as a yellow solid. LC-MS: 528.0 (M+H).

後処理

  1. customThe cooling bath was removed
  2. temperatureThe mixture was cooled to −78° C.
  3. additionwas added dropwise
  4. customThe cooling bath was removed
  5. stirringthe mixture stirred at RT for 18 h
  6. additionThe mixture was diluted with saturated NH4Cl
  7. extractionextracted with ethyl acetate
  8. washthe organic layer washed with water, brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customto give a material which
  12. customwas purified by silica gel chromatography

出典と根拠

ORDレコード
ord-e7f62fef4e4644f281f37e7a031c19bf
出典データセット
uspto-grants-2016_08
特許番号
US09409888B2

反応ノート

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