Sodium hydride → 4-[(3-Ethoxycarbonyl-propyl)-isopropoxycarbonyl-amino]-indan-5-carboxylic acid methyl ester

HRID 507068Notes

Reaction equation

HRID 507068 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([NH:14][C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10][CH2:9][CH2:8]2)=[O:4].[H-].[Na+].Br[CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28]>CN(C)C=O.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[C:6]([N:14]([CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10][CH2:9][CH2:8]2)=[O:4]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 76300Ethyl 4-bromobutyrateHCID 593791344-Isopropoxycarbonylamino-indan-5-carboxylic acid methyl ester

Product 1

HCID 593791374-[(3-Ethoxycarbonyl-propyl)-isopropoxycarbonyl-amino]-indan-5-carboxylic acid methyl esterYield 81%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

Add a solution of 4-isopropoxycarbonylamino-indan-5-carboxylic acid methyl ester (570 mg, 2.1 mmol) in dimethylformamide (8.2 mL) to a suspension of sodium hydride 60% dispersion mineral oil (82 mg, 2.1 mmol) in dimethylformamide (8.2 mL) at 0° C. under an atmosphere of nitrogen and allow to reach room temperature over 1 h. Add ethyl 4-bromobutyrate (0.44 mL, 3.09 mmol) and stir at room temperature for 14 h, then heat at 65° C. for 2 h. Cool the mixture to room temperature, dilute with ethyl acetate, wash with 1M HCl, water, and brine. Dry the organic layer over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to provide the title compound (651 mg, 81%). 1H NMR (MeOD, 300 MHz) δ 1.03-1.34 (m, 9H), 1.85 (m, 2H), 2.10 (m, 2H), 2.30 (m, 2H), 2.82-3.01 (m, 4H), 3.32 (m, 1H), 3.68 (m, 1H), 3.86 (s, 3H), 4.08 (m, 2H), 4.91 (m, 1H), 7.19 (d, J=7.7 Hz, 1H), 7.77 (d, J=7.7 Hz, 1H). MS (ES+): 392 (M+H).

Workup

  1. temperatureCool the mixture to room temperature
  2. washwash with 1M HCl, water, and brine
  3. dry with materialDry the organic layer over anhydrous sodium sulfate
  4. filtrationfilter
  5. customremove the solvent under reduced pressure
  6. customPurify the residue by flash chromatography
  7. washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-1433ad17d38f404b8dce6f9eec8efd81
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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