Aluminium lithium hydride → 1-(4-Chlorophenyl)-3-[1-[3-(1-hydroxyethyl)phenyl]-1-methyl-ethyl]urea

HRID 64224Notes

Reaction equation

HRID 64224 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([C:10]([NH:13][C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)=[O:15])([CH3:12])[CH3:11])[CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([NH:16][C:14]([NH:13][C:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([CH:1]([OH:3])[CH3:2])[CH:5]=2)([CH3:12])[CH3:11])=[O:15])=[CH:18][CH:19]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 70850877HCID 70850877, compound

Product 1

HCID 714572001-(4-Chlorophenyl)-3-[1-[3-(1-hydroxyethyl)phenyl]-1-methyl-ethyl]ureaYield 81.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-(2-(3-acetylphenyl)propan-2-yl)-3-(4-chlorophenyl)urea (25 mg, 0.07 mmol) in THF was cooled in an ice bath to 0° C. Lithium aluminum hydride solution (2 M in THF, 0.8 equiv) was added drop wise over 5 min and then the reaction was continued for approximately 1 h at 0° C. until starting material disappeared. The reaction was carefully quenched with a solution of sodium sulfate. The reaction mixture was filtered through a sintered funnel and the supernatant washed with dichloromethane. Combined organic fractions were concentrated under reduced pressure. The residue was purified by column chromatography using chloroform-methanol as a eluent to give 10 (19 mg, 74%). 1H NMR (DMSO-d6, 400 MHz) δ 1.25 (d, J=6 Hz, 3H), 1.54 (s, 6H), 4.64 (pent, J=4.4 Hz, 1H), 5.09 (d, J=4 Hz, 1H), 6.56 (s, 1H), 7.11-7.19 (m, 5H), 7.28 (s, 1H), 7.31 (d, J=9.2 Hz, 1H), 8.51 (s, 1H); 13C NMR (DMSO-d6, 100 MHz) δ 26.78, 30.33, 30.44, 55.06, 68.94, 119.47, 122.42, 123.70, 124.88, 128.28, 129.10, 140.18, 147.68, 148.65, 154.48; ESI-HRMS for C18H22N2O2Cl (M+H)+ calcd. 333.1370. found 333.1378.

Workup

  1. customThe reaction was carefully quenched with a solution of sodium sulfate
  2. filtrationThe reaction mixture was filtered through a sintered funnel
  3. washthe supernatant washed with dichloromethane
  4. concentrationCombined organic fractions were concentrated under reduced pressure
  5. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-a3cbef0f3e3d4b9495c3acc5f7283df2
Source dataset
uspto-grants-2016_09
Patent number
US09447134B2

Reaction notes

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