4-Nitrobenzoic Acid → HCID 178454134, compound

HRID 707269Notes

Reaction equation

HRID 707269 reaction equation
[OH:1][C@H:2]1[CH2:5][C@H:4]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:3]1.[N+:14]([C:17]1[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][CH:18]=1)([O-:16])=[O:15].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(/C(OC(C)C)=O)=N\C(OC(C)C)=O>C1COCC1>[N+:14]([C:17]1[CH:18]=[CH:19][C:20]([C:21]([O:1][C@H:2]2[CH2:3][C@H:4]([NH:6][C:7]([O:8][C:9]([CH3:10])([CH3:12])[CH3:11])=[O:13])[CH2:5]2)=[O:22])=[CH:24][CH:25]=1)([O-:16])=[O:15]

Participants

6

Reactant 4

HCID 61084-Nitrobenzoic AcidHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 178454126HCID 178454126, compound

Product 1

HCID 178454134HCID 178454134, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of racemic (2:1) in favor of trans tert-butyl (3-hydroxycyclobutyl)carbamate (16.8 g, 90 mmol) and 4-nitrobenzoic acid (10.97 ml, 102 mmol) in THF (300 mL) were added triphenyl phosphorus (30.0 ml, 130 mmol) and (E)-diisopropyl diazene-1,2-dicarboxylate (25 ml, 124 mmol) dropwise at 0° C. The resulting mixture was stirred at room temperature for 18 h. The reaction was concentrated and the crude material purified by flash silica gel chromatography on ISCO eluting with 0-40% EtOAc/hexanes to give a mixture cis and trans products. The mixture of isomers was purified by chiral separation to give the desired trans isomer trans-3-((tert-butoxycarbonyl)amino)cyclobutyl 4-nitrobenzoate (17.4 g, 51.7 mmol, 87% yield).

Workup

  1. concentrationThe reaction was concentrated
  2. customthe crude material purified by flash silica gel chromatography on ISCO
  3. washeluting with 0-40% EtOAc/hexanes
  4. customto give a mixture cis and trans products
  5. additionThe mixture of isomers
  6. customwas purified by chiral separation

Sources & evidence

ORD record
ord-772df033ee73400b9549117b8e20c988
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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