Water → ethyl[(1S)-5-(3-bromopropoxy)-2,3-dihydro-1H-inden-1-yl]acetate

HRID 603390노트

반응식

HRID 603390 반응식
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@H:7]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:6][CH2:5]2.O.[Br:18][CH2:19][CH2:20][CH2:21]Br.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[Br:18][CH2:19][CH2:20][CH2:21][O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@H:7]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:6][CH2:5]2

참가 물질

6

반응물 4

HCID 962WaterHCID 80011,3-DibromopropaneHCID 10796Cesium carbonateHCID 16110404ethyl 2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate

생성물 1

HCID 16110497ethyl[(1S)-5-(3-bromopropoxy)-2,3-dihydro-1H-inden-1-yl]acetate수율 60%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of ethyl [(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate (0.166 g, 0.754 mmol) (Example 6) in DMF (0.5 mL, containing 1% v/v of water), were added 1,3-dibromopropane (0.27 mL, 2.64 mmol) and Cs2CO3 (0.295 g, 0.905 mmol). The mixture was stirred at rt for 13 h and then at 80° C. for 1 h. Upon cooling to rt, the reaction mixture was concentrated under reduced pressure. The residue was suspended in EtOAc, filtered, and the filter cake was washed with EtOAc. The combined filtrate was dried, concentrated and purified by silica gel chromatography (100% hexanes to EtOAc/hexane (v/v) 1:19 gradient) to give 153 mg (60%) of the title compound containing minor impurities. This material was used in later steps without further purification. 1H NMR (300 MHz, CDCl3): δ 7.08 (d, 1H), 6.78 (s, 1H), 6.70 (dd, 1H), 4.19 (q, 2H), 4.08 (t, 2H), 3.60 (t, 2), 3.58-3.44 (m, 1H), 2.96-2.64 (m, 3H), 2.50-2.21 (m, 4H), 1.93-1.68 (m, 1H), 1.28 (t, 3H).

후처리

  1. waitat 80° C. for 1 h
  2. temperatureUpon cooling to rt
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. filtrationfiltered
  5. washthe filter cake was washed with EtOAc
  6. customThe combined filtrate was dried
  7. concentrationconcentrated
  8. custompurified by silica gel chromatography (100% hexanes to EtOAc/hexane (v/v) 1:19 gradient)

출처 및 근거

ORD 기록
ord-5a8c197d309846c7bd44a2eaf0fa7f9c
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07906653B2

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