Isopropanol → Hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one

HRID 2353440Notes

Reaction equation

HRID 2353440 reaction equation
C(O[C:6]([NH:8][CH:9]1[CH:13]([O:14]S(C)(=O)=O)[CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10]1)=[O:7])(C)(C)C.O=C1NC2CN(C(OC(C)(C)C)=O)CC2O1.C(O)(C)C.FC(F)(F)C(O)=O.C(Cl)Cl>ClC(Cl)C>[O:14]1[CH:13]2[CH2:12][NH:11][CH2:10][CH:9]2[NH:8][C:6]1=[O:7]

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 21863450Trifluoroacetic acid methylene chlorideHCID 68717764HCID 68717764, compoundHCID 77231323HCID 77231323, compound

Product 1

HCID 58333992Hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of tert-butyl 3-[(tert-butoxycarbonyl)amino]-4-[(methylsulfonyl)oxy]pyrrolidine-1-carboxylate (850 mg) in dichloroethane (50 mL) was refluxed overnight, evaporated and the resulting residue purified on a Biotage Horizon® system (silica, gradient 10-15% methanol in dichloromethane) to yield a racemic mixture of tert-butyl 2-oxohexahydro-5H-pyrrolo[3,4-d][1,3]oxazole-5-carboxylate which was resolved by chiral HPLC (Chiralcel OJ column, isopropyl alcohol/hexptane 13:87) to yield fast moving isomer A and slow moving isomer B. Each of isomer A and isomer B was treated with trifluoroacetic acid/methylene chloride (1:1) and passed through ion exchange resin (Strata-X-C™) and eluted with methanol containing 5% ammonium hydroxide to yield hexahydro-2H-pyrrolo[3,4-d][1,3]oxazol-2-one isomer A2 and isomer B2, respectively.

Workup

  1. customevaporated
  2. customthe resulting residue purified on a Biotage Horizon® system (silica, gradient 10-15% methanol in dichloromethane)
  3. customto yield
  4. customto yield fast
  5. washeluted with methanol containing 5% ammonium hydroxide

Sources & evidence

ORD record
ord-9f7de0615d9e4735a87ffc5bd1bfe33b
Source dataset
uspto-grants-2010_07
Patent number
US07750034B2

Reaction notes

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