Ethyl chloroformate → HCID 11717921, compound

HRID 1994294Notes

Reaction equation

HRID 1994294 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:19][CH2:18][N:17]([CH:20]([CH:24]([CH3:26])[CH3:25])[C:21](O)=[O:22])[C:16]2=[O:27])=[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:45][NH2:46]>C1COCC1.CCOC(C)=O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:19][CH2:18][N:17]([CH:20]([CH:24]([CH3:25])[CH3:26])[C:21]([NH:46][OH:45])=[O:22])[C:16]2=[O:27])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 10928Ethyl chloroformateHCID 81531DiisopropylethylamineHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 68536501HCID 68536501, compound

Product 1

HCID 11717921HCID 11717921, compoundYield 33.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(3-(4-Benzyloxyphenyl)-2-oxoimidazolidin-1-yl)-3-methylbutyric acid (66 mg; 0.18 mmol) was dissolved in THF (2 ml). At 0° C., diisopropylethylamine (DIEA; 124 μl; 0.71 mmol) and ethyl chloroformate (51 μl; 0.53 mmol) were successively added. The mixture was allowed to reach RT from 0° C. over the course of 2 h and then O-trimethylsilylhydroxylamine (80.43 μl; 1.07 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-benzyloxyphenyl)-2-oxoimidazolidin-1-yl)-N-hydroxy-3-methylbutyramide (22 mg; 0.06 mmol). MS: 384.25 (M+H); Rt: 1.94 min (method: gradient acetonitrile+0.08% formic acid: H2O+0.1% formic acid from 5:95 (0 min) to 95:5 (2.5 min) to 95:5 (3 min); flow rate 1.3 ml/min; column YMC Jsphere 33*2.1)

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-564bbd7c7d11420fae993a3418b7e779
Source dataset
uspto-grants-2010_01
Patent number
US07652143B2

Reaction notes

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