Acetic Acid → HCID 86618155, compound

HRID 2246594Notes

Reaction equation

HRID 2246594 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][CH2:15][N:14]([C@H:17]2[CH2:22][CH2:21][C@@H:20]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19][C@H:18]2C(N)=O)[C:13]1=[O:34])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.C(O)(=O)C.CC#[N:56]>O>[NH2:56][C@H:18]1[C@@H:17]([N:14]2[CH2:15][CH2:16][C@H:12]([NH:11][C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[O:10])[C:13]2=[O:34])[CH2:22][CH2:21][C@@H:20]([NH:23][C:24](=[O:25])[O:26][C:27]([CH3:30])([CH3:28])[CH3:29])[CH2:19]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6342AcetonitrileHCID 12217721Iodo benzene diacetateHCID 67181792(1R,2S,5R)-2-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)-5-(tert-butoxycarbonylamino)cyclohexanecarboxamide

Product 1

HCID 86618155HCID 86618155, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To the solution of (1R,2S,5R)-2-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)-5-(tert-butoxycarbonylamino)cyclohexanecarboxamide (2.0 g, 4.21 mmol; see Example 1, Step 5) in MeCN (150 mL) and H2O (205 mL), iodobenzene diacetate (1.357 g, 4.21 mmol) was added. The mixture was stirred at 0° C. for 1 h and then allowed to warm to room temperature in the melting ice bath over 14 h. The mixture was acidified to pH 4 with the addition of acetic acid, and then extracted with diethyl ether (2×60 mL). The aqueous layer was concentrated under reduced pressure to remove acetonitrile. The residual solution was extracted with methylene chloride (2×80 mL) after adjusting the pH to 9-10 using saturated NaHCO3. The methylene chloride layer was dried (Na2SO4) and concentrated in vacuo to give the desired tert-butyl (1R,3R,4S)-3-amino-4-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)cyclohexylcarbamate (1.8 g, 4.03 mmol, 96% yield). LC/MS found [M+H]+=447.

Workup

  1. extractionextracted with diethyl ether (2×60 mL)
  2. concentrationThe aqueous layer was concentrated under reduced pressure
  3. customto remove acetonitrile
  4. extractionThe residual solution was extracted with methylene chloride (2×80 mL)
  5. dry with materialThe methylene chloride layer was dried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-19b989e795794857aa9fb198b6254db8
Source dataset
uspto-grants-2010_03
Patent number
US07687508B2

Reaction notes

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