4-Chlorobenzoic Acid → HCID 67774379, compound

HRID 1808844Notes

Reaction equation

HRID 1808844 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:42][O:43][C@H:44]([CH3:54])[C@H:45]([NH:52][CH3:53])[CH2:46][N:47]1[CH2:50][CH:49]([OH:51])[CH2:48]1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:52]([C@@H:45]([C@H:44]([O:43][CH3:42])[CH3:54])[CH2:46][N:47]2[CH2:48][CH:49]([OH:51])[CH2:50]2)[CH3:53])=[O:8])=[CH:9][CH:10]=1

Participants

7

Reactant 5

HCID 63184-Chlorobenzoic AcidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67775924HCID 67775924, compound

Product 1

HCID 67774379HCID 67774379, compoundYield 28.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 4-chlorobenzoic acid (65.7 mg, 0.42 mmol) and DIPEA (0.365 mL, 2.10 mmol) in DCM (0.7 mL) was TBTU (148 mg, 0.46 mmol) added 1-((2R,3R)-3-Methoxy-2-(methylamino)butyl)azetidin-3-ol (Compound B2.2) (79 mg, 0.42 mmol) in DCM (0.7 mL) was added and the resultant mixture stirred at rt for 2 h. NaHCO3 was added and the stirring continued for 30 min. The layers were separated and the organic phase concentrated under reduced pressure. The residue was dissolved in THF/MeOH/water (3:1:1) and a small amount of NaOH (3.8M) was added. The resultant mixture was stirred for 30 min. The mixture was diluted with water and the organic solvent was removed. The water layer was extracted with DCM. The combined organic layers were filtered through a phase separator and concentrated. The residue was purified by preparative HPLC to give the title compound (39 mg, 28%). Mixture of rotamers: 1H NMR (600 MHz, DMSO-d6) δ 0.92, 1.08, 2.34-2.40, 2.52-2.59, 2.63, 2.69, 2.70-2.76, 2.77, 3.18-3.23, 3.34-3.39, 3.44-3.48, 3.48-3.54, 4.04-4.10, 4.11-4.16, 4.40, 5.16-5.24, 7.31, 7.40, 7.43-7.50. Total of protons in spectrum: 22. Ratio major:minor:3:2. HRMS (M+H)+: calculated 327.1475. found 327.1476.

Workup

  1. additionwas added
  2. customThe layers were separated
  3. concentrationthe organic phase concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in THF/MeOH/water (3:1:1)
  5. additiona small amount of NaOH (3.8M) was added
  6. additionThe mixture was diluted with water
  7. customthe organic solvent was removed
  8. extractionThe water layer was extracted with DCM
  9. filtrationThe combined organic layers were filtered through a phase separator
  10. concentrationconcentrated
  11. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-64d49afa044f46248071238071465966
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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