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

HRID 2235886Notes

Reaction equation

HRID 2235886 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:10]([O:12][C:13](=[O:29])[CH2:14][C@H:15]1[C:23]2[C:18](=[CH:19][C:20]([O:24][CH2:25][CH2:26][CH2:27]Br)=[CH:21][CH:22]=2)[CH2:17][CH2:16]1)[CH3:11].[NH4+].[Cl-]>CN(C=O)C>[NH:1]([CH2:27][CH2:26][CH2:25][O:24][C:20]1[CH:19]=[C:18]2[C:23](=[CH:22][CH:21]=1)[C@H:15]([CH2:14][C:13]([O:12][CH2:10][CH3:11])=[O:29])[CH2:16][CH2:17]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6115AnilineHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 16110497ethyl[(1S)-5-(3-bromopropoxy)-2,3-dihydro-1H-inden-1-yl]acetate

Product 1

HCID 59300513ethyl [(1S)-5-(3-anilinopropoxy)-2,3-dihydro-1H-inden-1-yl]acetateYield 9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of aniline (273 mg, 2.93 mmol) in DMF (4 mL) under argon was added sodium hydride (117 mg, 2.93 mmol, 60% dispersion in mineral oil), and the mixture was stirred under argon for 20 min. A solution of ethyl [(1S)5-(3-bromopropoxy)-2,3-dihydro-1H-inden-1-yl]acetate (Example 45, 500 mg, 1.47 mmol) in DMF (4 mL) was added and the reaction mixture was stirred for 24 h at rt. A saturated aqueous NH4Cl solution was added, and the solvents were evaporated under vacuum. The residue was suspended in EtOAc and filtered through a small silica gel plug. The filtrate was concentrated under reduced pressure and then purified by silica gel chromatography (5-10% EtOAc in hex) to give the title compound (44 mg, 9%) as an oil containing minor impurities. 1H NMR (400 MHz, CDCl3): δ 7.11-6.92 (m, 3H), 6.68-6.48 (m, 5H), 4.12-3.93 (m, 4H), 3.50-3.37 (br, 1H), 3.22 (t, 2H), 2.85-2.68 (m, 2H), 2.62 (dd, 1H), 2.38-2.23 (m, 2H), 2.04-1.96 (m, 2H), 1.72-1.60 (m, 1H), 1.08 (t, 3H).

Workup

  1. stirringthe reaction mixture was stirred for 24 h at rt
  2. customthe solvents were evaporated under vacuum
  3. filtrationfiltered through a small silica gel plug
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. custompurified by silica gel chromatography (5-10% EtOAc in hex)

Sources & evidence

ORD record
ord-f8f67deebc0543ea859b895740fa46d7
Source dataset
uspto-grants-2010_05
Patent number
US07714004B2

Reaction notes

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