1-[2-(4-Bromophenoxy)ethyl]piperidine → (+)-1-[3-Hydroxy-6-[4-(2-piperidin-1-yl-ethoxy)phenyl]-6h-benzo[c]chromen-8-yl]-ethanone

HRID 1359148노트

반응식

HRID 1359148 반응식
Br[C:2]1[CH:16]=[CH:15][C:5]([O:6][CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.C([Li])CCC.C[O:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]3[CH:38]=[CH:37][C:36]([C:39]4([CH3:44])OCC[O:40]4)=[CH:35][C:29]=3[C:30](=O)[O:31]2)=[CH:26][CH:25]=1.[Li]>C1COCC1.O>[OH:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]3[CH:38]=[CH:37][C:36]([C:39](=[O:40])[CH3:44])=[CH:35][C:29]=3[CH:30]([C:2]3[CH:16]=[CH:15][C:5]([O:6][CH2:7][CH2:8][N:9]4[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]4)=[CH:4][CH:3]=3)[O:31]2)=[CH:26][CH:25]=1

참가 물질

7

반응물 4

HCID 8671951-[2-(4-Bromophenoxy)ethyl]piperidine2회HCID 3028194LithiumHCID 113244043-Methoxy-8-(2-methyl-[1,3]-dioxolan-2-yl)-benzo[c]chromen-6-oneHCID 178418339Butyllithium

생성물 1

HCID 11374158(+)-1-[3-Hydroxy-6-[4-(2-piperidin-1-yl-ethoxy)phenyl]-6h-benzo[c]chromen-8-yl]-ethanone수율 48%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

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온도
-78 °C

실험 절차

1-[2-(4-bromo-phenoxy)-ethyl]-piperidine (0.76 g, 2.7 mmol) from Step F was dissolved in THF (15 ml) under Ar and cooled to −78° C. n-Butyl lithium (10.0 M, 0.26 ml, 2.6 mmol) was added and the mixture was stirred at −78° C. for 1 hour. The compound from Step E (1.11 g, 3.56 mmol) was dissolved in THF (35 ml) under Ar and cooled to −78° C. to which the freshly prepared lithium salt of 1-(2-(4-bromo-phenoxy)-ethyl)-piperidine was transferred via a cannula. The reaction was stirred for 2 h. Water (150 ml) was added and the reaction extracted three times with ethyl acetate (150 ml). After removing the solvent the crude product was chromatographed on silica gel with 7% CH3OH/CH2Cl2 to yield 0.56 g (48%) of the title compound. 1H-NMR (400 MHz, CDCl3) δH 1.44 (2H, m, NCH2CH2CH2), 1.59 (4H, m, NCH2CH2CH2) 1.61 (3H, s, CH3), 2.25 (4H, m, NCH2CH2CH2), 2.83 (2H, m, NCH2CH2O), 3.78 (2H, m, OCH2), 3.85 (3H, s, OCH3), 4.01 (2H, m, OCH2), 4.18 (2H, m, NCH2CH2O), 6.69 (1H, s, ArH), 6.73 (1H, d, ArH), 6.96 (2H, d, ArH), 7.17 (1H, s, ArH), 7.56 (1H, m, ArH), 7.60 (2H, d, ArH), 7.76 (2H, m, ArH).

후처리

  1. additionwas added
  2. stirringThe reaction was stirred for 2 h
  3. extractionthe reaction extracted three times with ethyl acetate (150 ml)
  4. customAfter removing the solvent the crude product
  5. customwas chromatographed on silica gel with 7% CH3OH/CH2Cl2

출처 및 근거

ORD 기록
ord-12f7047f8ecf414fa7f70b8e77c55f5a
출처 데이터셋
uspto-grants-2003_07
특허 번호
US06599921B2

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