Toluene → HCID 57495614, compound

HRID 1092303Notes

Reaction equation

HRID 1092303 reaction equation
CO[C:3](=[O:28])[CH:4]([N:11]([CH:25]([CH3:27])[CH3:26])[C:12]([NH:14][CH:15]1[CH:22]2[CH2:23][CH:18]3[CH2:19][CH:20]([CH2:24][CH:16]1[CH2:17]3)[CH2:21]2)=[O:13])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C1(C)C=CC=CC=1.C(OCC)(=O)C.C12CC3CC(CC(C3)C1N1C=C(C3C=CC=CC=3)N(C(C)C)C1=O)C2>C(Cl)Cl.CCCCCCC.C(Cl)Cl.CC#N>[CH:22]12[CH2:23][CH:18]3[CH2:19][CH:20]([CH2:24][CH:16]([CH2:17]3)[CH:15]1[N:14]1[C:3](=[O:28])[CH:4]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:11]([CH:25]([CH3:26])[CH3:27])[C:12]1=[O:13])[CH2:21]2

Participants

8

Reactant 4

HCID 1140TolueneHCID 8857Ethyl AcetateHCID 24964067HCID 24964067, compoundHCID 66593066HCID 66593066, compound

Product 1

HCID 57495614HCID 57495614, compoundYield 63.3%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8900HeptaneSolventHCID 21877088Acetonitrile methylene chlorideSolvent

Conditions

Temperature
-78 °C

Procedure

In this case, treatment of (3-adamantan-2-yl-1-isopropyl-ureido)-phenyl-acetic acid methyl ester with diisobutylaluminium hydride as described in example 1, step B] did not result in the formation of the desired material. Alternatively, (3-adamantan-2-yl-1-isopropyl-ureido)-phenyl-acetic acid methyl ester (200 mg) was dissolved in DCM (3 mL) and toluene (3 mL) under argon and treated with sodium dihydrido-bis-(2-methoxyethoxy)-aluminate (Red-Al™, 3.5 M in toluene, 0.09 mL) at −78° C. After addition of the reducing agent, the mixture was stirred at −78° C. for 30 minutes and was then allowed to warm to 0° C. The reaction mixture was quenched with 1M potassium sodium tartrate solution (10 mL) and then poured into 25% HCl (25 mL) containing a small amount of ice. The aqueous mixture was saturated with NaCl and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over Na2SO4, and evaporated to give a crude product. This material was subjected to flash chromatography using a gradient of 10 to 40% ethyl acetate in heptane followed by a second flash chromatography using DCM and by DCM/CH3CN 9:1 as eluents. This procedure provided 3-adamantan-2-yl-1-isopropyl-5-phenyl-imidazolidine-2,4-dione (116 mg) as the major product whereas the desired material 1-adamantan-2-yl-3-isopropyl-4-phenyl-1,3-dihydro-imidazol-2-one was obtained as the minor component (colorless oil, 14 mg). MS (EI): 336.2 (M+).

Workup

  1. additionAfter addition of the reducing agent
  2. temperatureto warm to 0° C
  3. customThe reaction mixture was quenched with 1M potassium sodium tartrate solution (10 mL)
  4. additionpoured into 25% HCl (25 mL)
  5. additioncontaining a small amount of ice
  6. extractionextracted with ethyl acetate
  7. customThe organic layer was separated
  8. washwashed with brine
  9. dry with materialdried over Na2SO4
  10. customevaporated
  11. customto give a crude product

Sources & evidence

ORD record
ord-7a49fac764af4b9982bcaa7ddea2aaec
Source dataset
uspto-grants-2012_03
Patent number
US08129423B2

Reaction notes

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