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

HRID 603390Notes

Reaction equation

HRID 603390 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-5a8c197d309846c7bd44a2eaf0fa7f9c
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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