tert-Butyl (4-bromonaphthalen-1-yl)carbamate → HCID 68230824、化合物

HRID 571110

反応式

HRID 571110 の反応式
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=1.C([Li])CCC.[CH:25]([C:27]1[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH:28]=1)=[O:26]>C1COCC1>[C:15]([O:14][C:13]([NH:12][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([CH:25]([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:40])[CH:28]=2)[OH:26])=[CH:3][CH:4]=1)=[O:19])([CH3:18])([CH3:17])[CH3:16]

参加物

5

反応物 3

HCID 11602218tert-Butyl (4-bromonaphthalen-1-yl)carbamateHCID 21306993tert-Butyl (4-formylpyridin-2-yl)carbamateHCID 178418339Butyllithium

生成物 1

HCID 68230824HCID 68230824、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To a stirred solution of tert-butyl (4-bromonaphthalen-1-yl)carbamate (WO 2006/010082) (2.09 g, 6.48 mmol) in dry THF (50 mL) under N2 at −78° C. was added n-butyllithium (2.5 M in hexanes, 5.5 mL, 13.8 mmol) over 15 mins. The resulting mixture was maintained at −78° C. for 1.5 hr and then treated with a solution of tert-butyl (4-formylpyridin-2-yl)carbamate (WO 2004/000831) (960 mg, 4.30 mmol) in dry THF (10 mL) in one portion. The reaction mixture was stirred at −78° C. for a further 1 hr and then warmed to RT for 18 hr. The mixture was cooled to 0° C. and the reaction was quenched by the addition of MeOH (5.0 mL), then warmed to RT and partitioned between EtOAc and water. The aq layer was separated and was extracted twice with EtOAc and the combined organic extracts were washed with brine and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 80 g, EtOAc in isohexane, 0-60%, gradient elution) to afford the title compound, Intermediate F1, as a pale yellow solid (1.13 g, 88% purity (LCMS), 49%); Rt 2.22 min (Method 2); m/z 466 (M+H)+ (ES+). The material so obtained was used in the next step without further purification.

後処理

  1. temperaturewarmed to RT for 18 hr
  2. temperatureThe mixture was cooled to 0° C.
  3. customthe reaction was quenched by the addition of MeOH (5.0 mL)
  4. temperaturewarmed to RT
  5. custompartitioned between EtOAc and water
  6. customThe aq layer was separated
  7. extractionwas extracted twice with EtOAc
  8. washthe combined organic extracts were washed with brine
  9. customdried
  10. customevaporated in vacuo
  11. customThe residue was purified by flash column chromatography (SiO2, 80 g, EtOAc in isohexane, 0-60%, gradient elution)

出典と根拠

ORDレコード
ord-c8d00e047b2d4042a42a771bb4946ced
出典データセット
uspto-grants-2015_05
特許番号
US09024041B2

関連ノート

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