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

HRID 2353937Notes

Reaction equation

HRID 2353937 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=O)C.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 DMF (8.2 mL) to a suspension of sodium hydride 60% dispersion mineral oil (82 mg, 2.1 mmol) in DMF (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-999a5646762c4524891d540daf4771e8
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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