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

HRID 603416Notes

Reaction equation

HRID 603416 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[C@H:20]([CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:19][CH2:18]2.[NH4+].[Cl-]>CN(C=O)C>[NH:1]([CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[C@H:20]([CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:19][CH2:18]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-88bdf3e04d4f47b591a863d5f96ee17e
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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