Benzofuran → HCID 18517728, compound

HRID 1368957Notes

Reaction equation

HRID 1368957 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1.C([Li])CCC.CON(C)[C:18]([CH:20]([NH:29][C:30]([CH:32]([NH:37][C:38](=[O:47])[O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:33][CH:34]([CH3:36])[CH3:35])=[O:31])[CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:19]>CCOCC>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:18]([CH:20]([NH:29][C:30]([CH:32]([NH:37][C:38](=[O:47])[O:39][CH2:40][C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)[CH2:33][CH:34]([CH3:36])[CH3:35])=[O:31])[CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:19]

Participants

5

Reactant 3

HCID 9223BenzofuranHCID 54260837HCID 54260837, compoundHCID 178418339Butyllithium

Product 1

HCID 18517728HCID 18517728, compoundYield 20.3%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-15 °C

Procedure

A solution comprised of benzofuran (0.302 g, 2.56 mmol) in anhydrous ether (5 mL) was cooled to −15° C. under a nitrogen atmosphere and then a solution of n-butyllithium (1.6 mL in hexanes) was added dropwise over 2 minutes. The mixture was stirred for 1 hour and then a solution comprised of benzyl 1-[1-(N-methoxy-N-methylcarbamoyl)-3-phenylpropylcarbamoyl]-3-methylbutylcarbamate (0.3 g, 0.64 mmol) in diethyl ether was added. The mixture was stirred at −15° C. until the reaction was complete. The mixture was quenched with a solution of acetic acid (0.153 mL) in diethyl ether (50 mL). The organic phase was washed with brine (40 mL), dried (MgSO4) and concentrated in vacuo. The product was purified from the residue by flash chromatography eluting with 2:3 ethyl acetate/hexanes to provide benzyl 1-[1-(benzofur-2-ylcarbonyl)-3-phenylpropylcarbamoyl]-3-methylbutylcarbamate (70 mg, 0.13 mmol) as a white solid. 1H NMR (CDCl3): δ 0.8-0.99 (d, J=4 Hz, 6H), 1.5 (m, 1H), δ 1.6-1.72 (m, 2H), δ 1.99-2.18 (m, 1H), δ 2.22-2.41 (m, 1H), δ 2.6-2.75 (m, 2H), δ 4.21 (m, 1H), δ 5.01 (m, 1H), δ 5.17 (s, 2H), δ 5.50 (m, 1H), δ 6.75-6.81 (d, J=7 Hz, 1H), δ 7.10-7.37 (m, 11H) 7.4-7.59(m, 3H), δ 7.64 (d, J=7 Hz, 1H). (C32H34N2O5).

Workup

  1. additionwas added
  2. stirringThe mixture was stirred at −15° C. until the reaction
  3. customThe mixture was quenched with a solution of acetic acid (0.153 mL) in diethyl ether (50 mL)
  4. washThe organic phase was washed with brine (40 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe product was purified from the residue by flash chromatography
  8. washeluting with 2:3 ethyl acetate/hexanes

Sources & evidence

ORD record
ord-95d670bf7ad74fe990b70091e91c4919
Source dataset
uspto-grants-2003_06
Patent number
US06576630B1

Reaction notes

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