tert-Butyl (4-bromonaphthalen-1-yl)carbamate → HCID 68230824, 화합물

HRID 571110

반응식

HRID 571110 반응식
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]

참가 물질

5

반응물 3

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

생성물 1

HCID 68230824HCID 68230824, 화합물

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-c8d00e047b2d4042a42a771bb4946ced
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09024041B2

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