Ethyl Acetate → HCID 68767765, compound

HRID 1374283Notes

Reaction equation

HRID 1374283 reaction equation
[C:1]([O:5][C:6](=[O:36])[NH:7][C@@H:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15](=[O:32])[C@@H:16]([NH:21][C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:17][CH2:18]SC)[C@H:10]([CH2:33][CH2:34][CH3:35])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].CCOC(C)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH2:25]([O:24][C:22](=[O:23])[NH:21][C@H:16]1[CH2:17][CH2:18][N:14]([C@H:11]2[CH2:12][CH2:13][C@@H:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:36])[CH2:9][C@H:10]2[CH2:33][CH2:34][CH3:35])[C:15]1=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 68769570(1R,3R,4S)-[4-((2S)-2-benzyloxycarbonylamino-4-methylsulfanyl-butyrylamino)-3-propyl-cyclohexyl]-carbamic acid tert-butyl ester

Product 1

HCID 68767765HCID 68767765, compoundYield 54.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The compound (1R,3R,4S)-[4-((2S)-2-benzyloxycarbonylamino-4-methylsulfanyl-butyrylamino)-3-propyl-cyclohexyl]-carbamic acid tert-butyl ester (375 mg) was “wetted” with EtOAc, and then the majority of EtOAc was removed under nitrogen stream. The residue was dissolved in iodomethane (6 mL), and the resulting solution was stirred at RT for 48 h before being concentrated in vacuo. The residue was dissolved in methylene chloride, and the resulting solution was concentrated; this was repeated to afford the salt. MS found: (M+H)+=536.3. This material was dissolved in DMF (12 mL) and the solution was charged with Cs2CO3 (470 mg, 1.4 mmol) and stirred for 12 h at RT before being partitioned between EtOAc and brine. The organic phase was dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford {(3S)-1-[(1S,2R,4R)-4-tert-butoxycarbonylamino-2-propyl-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-carbamic acid benzyl ester (185 mg). MS found: (M+H)+=474.3.

Workup

  1. customthe majority of EtOAc was removed under nitrogen stream
  2. dissolutionThe residue was dissolved in iodomethane (6 mL)
  3. concentrationbefore being concentrated in vacuo
  4. dissolutionThe residue was dissolved in methylene chloride
  5. concentrationthe resulting solution was concentrated
  6. customto afford the salt
  7. stirringstirred for 12 h at RT
  8. custombefore being partitioned between EtOAc and brine
  9. dry with materialThe organic phase was dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-dc322338bd484ac1ab8c2529d6350f72
Source dataset
uspto-grants-2007_01
Patent number
US07163937B2

Reaction notes

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