Iodoethane → 1,1-Dimethylethyl 3-ethyl-1-methyl-2-oxo-4-imidazolidinecarboxylate

HRID 2081036Notes

Reaction equation

HRID 2081036 reaction equation
[CH3:1][N:2]1[CH2:6][CH:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[NH:4][C:3]1=[O:14].O=C1N(C(OCC2C=CC=CC=2)=O)[C@H:19](C(O)=O)[CH2:18]N1.ICC.[H-].[Na+]>CN(C)C=O>[CH2:18]([N:4]1[CH:5]([C:7]([O:9][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:8])[CH2:6][N:2]([CH3:1])[C:3]1=[O:14])[CH3:19]

Participants

6

Reactant 4

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 688196(S)-(-)-2-Oxo-1,5-imidazolidinedicarboxylic acid 1-benzyl esterHCID 130539751,1-Dimethylethyl 1-methyl-2-oxo-4-imidazolidinecarboxylate

Product 1

HCID 671037011,1-Dimethylethyl 3-ethyl-1-methyl-2-oxo-4-imidazolidinecarboxylateYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-10 °C

Procedure

A stirred solution of 1,1-dimethylethyl 1-methyl-2-oxo-4-imidazolidinecarboxylate (0.501 g, 2.5 mmol) (prepared as described in step (i) of Example 49 from 5-(1,1-dimethylethyl)1-(phenylmethyl)3-methyl-2-oxo-1,5-imidazolidinedicarboxylate, itself prepared as described in step (ii) of Example 13, starting originally from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) in N,N-dimethylformamide (10 ml) was cooled to −10° C. under argon and treated with iodoethane (0.404 ml, 5.00 mmol). Sodium hydride (60% dispersion in oil) (0.100 g, 2.500 mmol) was added portion wise. The mixture was allowed stirred warm to room temperature over 3 hours. The solvent was evaporated in vacuo and the residue was partitioned between ethyl acetate (20 ml) and brine (10 ml). The aqueous layer was re-extracted with ethyl acetate (20 ml) and the organic extracts were combined, washed with saturated sodium hydrogen carbonate solution (20 ml), water (2×20 ml) and brine (20 ml), dried and evaporated. The residue was purified by silica gel chromatography eluting with 25-100% ethyl acetate in isohexane to give 1,1-dimethylethyl 3-ethyl-1-methyl-2-oxo-4-imidazolidinecarboxylate (433 mg, 76%). LC/MS [M+H]+=229. (ii) A solution of 1,1-dimethylethyl 3-ethyl-1-methyl-2-oxo-4-imidazolidinecarboxylate (433 mg, 1.897 mmol) in TFA/DCM (1:2, 6 ml) was stirred at room temperature for 18 hours. The solution was evaporated and the residue was co-evaporated with dichloromethane and dried to give crude 3-ethyl-1-methyl-2-oxo-4-imidazolidinecarboxylic acid, (assume ˜1.9 mmol). LC/MS [M+H]+=173.

Workup

  1. customprepared
  2. temperaturewarm to room temperature over 3 hours
  3. customThe solvent was evaporated in vacuo
  4. customthe residue was partitioned between ethyl acetate (20 ml) and brine (10 ml)
  5. extractionThe aqueous layer was re-extracted with ethyl acetate (20 ml)
  6. washwashed with saturated sodium hydrogen carbonate solution (20 ml), water (2×20 ml) and brine (20 ml)
  7. customdried
  8. customevaporated
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with 25-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-f77694732db048098ac7ef993983e3fc
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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