Ethyl chloroformate → 2-(3-(4-benzyloxybenzyl)-2-oxoimidazolidin-1-yl)-N-hydroxy-3-methylbutyramide

HRID 1994292Notes

Reaction equation

HRID 1994292 reaction equation
[CH2:1]([O:8][C:9]1[CH:28]=[CH:27][C:12]([CH2:13][N:14]2[CH2:18][CH2:17][N:16]([CH:19]([CH:23]([CH3:25])[CH3:24])[C:20]([OH:22])=O)[C:15]2=[O:26])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.ClC(OCC)=O.C[Si](C)(C)[O:46][NH2:47]>O1CCCC1.CCOC(C)=O>[CH2:1]([O:8][C:9]1[CH:28]=[CH:27][C:12]([CH2:13][N:14]2[CH2:18][CH2:17][N:16]([CH:19]([CH:23]([CH3:25])[CH3:24])[C:20]([NH:47][OH:46])=[O:22])[C:15]2=[O:26])=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 10928Ethyl chloroformateHCID 81531DiisopropylethylamineHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 685390582-(3-(4-Benzyloxybenzyl)-2-oxoimidazolidin-1-yl)-3-methylbutyric acid

Product 1

HCID 115313772-(3-(4-benzyloxybenzyl)-2-oxoimidazolidin-1-yl)-N-hydroxy-3-methylbutyramideYield 46.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(3-(4-Benzyloxybenzyl)-2-oxoimidazolidin-1-yl)-3-methylbutyric acid (50 mg; 0.13 mmol) was dissolved in tetrahydrofuran (THF; 2 ml). At 0° C., diisopropylethylamine (DIEA; 69 μl; 0.39 mmol) and ethyl chloroformate (25 μl; 0.26 mmol) were successively added. The mixture was allowed to reach RT from 0° C. over the course of 2 h, and then O-trimethylsilylhydroxylamine (50 μl; 0.65 mmol) was added. Stirring at RT for a further 3 h was followed by partitioning between dilute HCl (10 ml) and EtOAc (10 ml). The phases were separated and the aqueous phase was extracted with EtOAc (3×; 5 ml). The combined organic phases were dried over MgSO4. The solvent was removed under reduced pressure. Trituration of the residue with EtOAc (2 ml) resulted in 2-(3-(4-benzyloxybenzyl)-2-oxoimidazolidin-1-yl)-N-hydroxy-3-methylbutyramide (25 mg; 0.06 mmol). MS: 398.15 (M+H); Rt: 1.30 min (method: gradient 0 min 96% H2O (0.05% TFA) 2.0 min 95% acetonitrile, 95% acetonitrile to 2.4 min, 4% acetonitrile 2.45 min; flow rate 1 ml/min; column 0.4 μL (YMC J'sphere ODS H80 20X2 1.4μ); 30° C.)

Workup

  1. customto reach RT from 0° C. over the course of 2 h
  2. customby partitioning between dilute HCl (10 ml) and EtOAc (10 ml)
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with EtOAc (3×; 5 ml)
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-6aa89c5335f342e99fd6d120f025ce0c
Source dataset
uspto-grants-2010_01
Patent number
US07652143B2

Reaction notes

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