o-Phenylbenzoic acid → HCID 67117099, compound

HRID 1193075Notes

Reaction equation

HRID 1193075 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH:13]2[CH:9]1[CH2:10][NH:11][CH2:12]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:16]([C:21](O)=[O:22])=[CH:17][CH:18]=[CH:19][CH:20]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH:13]2[CH:9]1[CH2:10][N:11]([C:21]([C:16]1[C:15]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:22])[CH2:12]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 70357o-Phenylbenzoic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 467381813,6-Diaza-bicyclo(3.2.0)heptane-6-carboxylic acid tert-butyl ester

Product 1

HCID 67117099HCID 67117099, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
23 °C

Procedure

Intermediate 18 (0.72 mmol), biphenyl-2-carboxylic acid (0.72 mmol), and HATU (1.66 mmol) were taken up in DMF at 0.2 M. DIPEA (2.17 mmol) was added. The mixture was allowed to stir at 23° C. for ˜1 hr. The mixture was diluted water and extracted with diethyl ether. The aqueous was extracted with ether again. The other fractions were combined and concentrated to provide the crude product. The product was purified on the silica gel chromatography (30-100% ethyl acetate/hexanes) over 12 minutes, then flushed with 100% ethyl acetate for 20 minutes to provide 3-(Biphenyl-2-carbonyl)-3,6-diaza-bicyclo[3.2.0]heptane-6-carboxylic acid tert-butyl ester, 91%. MS (ESI) mass calcd. for C23H26N2O3, 378.46; m/z found, 379.2 [M+H]+. This material was taken up in DCM and TFA was added. The mixture was allowed to stir at 23° C. for 1 hr. It was then concentrated after checking by MS and LCMS to provide a yellow viscous oil. The oil was taken up and DCM and 1M NaOH were added, and the resulting solution was allowed to stirred for 5 minutes. The layers were separated, and the organic layer was concentrated to provide Intermediate 19 as a light yellow foamy solid. MS (ESI) mass calcd. for C18H18N2O, 278.35; m/z found, 279.2 [M+H]+.

Workup

  1. extractionextracted with diethyl ether
  2. extractionThe aqueous was extracted with ether again
  3. concentrationconcentrated
  4. customto provide the crude product
  5. customThe product was purified on the silica gel chromatography (30-100% ethyl acetate/hexanes) over 12 minutes
  6. customflushed with 100% ethyl acetate for 20 minutes

Sources & evidence

ORD record
ord-22d722e544604fc4a7c9f28597ce4fef
Source dataset
uspto-grants-2014_03
Patent number
US08680275B2

Reaction notes

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