Urea → N-[2-(4-Carbomethoxyphenyl)-1-methylethyl]-2-hydroxy-2-(4-methyl-oxazol-5-yl)ethanamine dihydrochloride

HRID 1587914Notes

Reaction equation

HRID 1587914 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][O:5][C:6]=1[C:7](=[O:10])[CH2:8]Br.C(N(CC)C(C)C)(C)C.[C:20]([C:24]1[CH:29]=[CH:28][C:27]([CH2:30][CH:31]([NH2:33])[CH3:32])=[CH:26][CH:25]=1)([O:22][CH3:23])=[O:21].NC(N)=O.[BH4-].[Na+].C(Cl)[Cl:41]>CO>[ClH:41].[ClH:41].[C:20]([C:24]1[CH:29]=[CH:28][C:27]([CH2:30][CH:31]([NH:33][CH2:8][CH:7]([OH:10])[C:6]2[O:5][CH:4]=[N:3][C:2]=2[CH3:1])[CH3:32])=[CH:26][CH:25]=1)([O:22][CH3:23])=[O:21]

Participants

8

Reactant 6

HCID 1176UreaHCID 6344Dichloromethane2×HCID 81531DiisopropylethylamineHCID 4311764Sodium borohydrideHCID 15034329Methyl 4-(2-aminopropyl)benzoateHCID 199743052-Bromo-1-(4-methyloxazol-5-yl)ethanone

Product 1

HCID 14076231N-[2-(4-Carbomethoxyphenyl)-1-methylethyl]-2-hydroxy-2-(4-methyl-oxazol-5-yl)ethanamine dihydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
35 °C

Procedure

2.6 g (0.009 mol) of 4-Methyl-5-bromoacetyl-oxazole and 1.16 g (0.009 mol) of N,N-diisopropyl-ethylamine are dissolved in 50 ml of methylene chloride. This solution is added dropwise, within 20 minutes to 3.47 g (0.018 mol) of 2-(4-carbomethoxyphenyl)-1-methylethylamine in 100 ml of methylene chloride, and the mixture is stirred at room temperature for 2 hours and at 35° C. for 1 hour. The reaction solution is cooled in an ice bath, and 150 ml of methanol are added. Then, for the reduction of the resulting amino-ketone, 1 g of sodium borohydride is added in portions over 30 minutes, and the mixture is stirred at room temperature for 20 hours and then evaporated. Ice-water is then added to the residue, and the mixture is acidified with hydrochloric acid, made alkaline with concentrated aqueous ammonia and extracted with chloroform. The extract is dried over sodium sulphate, concentrated and purified on a silica gel column using ethyl acetate/methanol=9:1 as eluant. The hydrochloride is then precipitated with ethereal hydrochloric acid.

Workup

  1. temperatureThe reaction solution is cooled in an ice bath
  2. stirringthe mixture is stirred at room temperature for 20 hours
  3. customevaporated
  4. additionIce-water is then added to the residue
  5. extractionextracted with chloroform
  6. dry with materialThe extract is dried over sodium sulphate
  7. concentrationconcentrated
  8. custompurified on a silica gel column
  9. customThe hydrochloride is then precipitated with ethereal hydrochloric acid

Sources & evidence

ORD record
ord-a19ee8b0b066455ba882ce074933f8a0
Source dataset
uspto-grants-1993_06
Patent number
US05219852

Reaction notes

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