4-Chlorobenzoic Acid → HCID 67773377, compound

HRID 1808854Notes

Reaction equation

HRID 1808854 reaction equation
CCN(C(C)C)C(C)C.[Cl:10][C:11]1[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:42][NH:43][C@@H:44]([CH3:51])[CH2:45][N:46]1[CH2:49][CH:48]([OH:50])[CH2:47]1>C(Cl)Cl.C1COCC1>[Cl:10][C:11]1[CH:12]=[CH:13][C:14]([C:15]([N:43]([C@@H:44]([CH3:51])[CH2:45][N:46]2[CH2:49][CH:48]([OH:50])[CH2:47]2)[CH3:42])=[O:17])=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 63184-Chlorobenzoic AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67772035HCID 67772035, compound

Product 1

HCID 67773377HCID 67773377, compoundYield 16%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

DIPEA (0.200 mL, 1.15 mmol) was added to a stirred suspension of 4-chlorobenzoic acid (0.06 g, 0.38 mmol) and TBTU (0.123 g, 0.38 mmol) in DCM (2 mL) at rt. The suspension was stirred for 5 min before it was cooled on an ice-bath. A solution of (S)-1-(2-(methylamino)propyl)azetidin-3-ol (Compound M11) (0.06 g, 0.42 mmol) in THF (1.5 mL) was added over 10 min. The ice-bath was removed and the reaction was stirred at rt over night. DCM (3 mL) was added and the mixture was washed with NaHCO3 (8% aq., 3 mL), filtered through a phase separator and concentrated under reduced pressure. The residue was dissolved in MeOH (2 mL) and NaOH (aq., 2M) was added. The resulting mixture was stirred at rt for 3 h, then concentrated under reduced pressure. DCM (5 mL) and NaHCO3, (aq., 8%, 5 mL) was added. The organic phase was collected and the solvents were removed under reduced pressure. The residue was purified by preparative HPLC to give the title compound (17 mg, 16%). Mixture of rotamers: 1H NMR (600 MHz, DMSO-d6) δ 0.99-1.12, 2.18-2.23, 2.33-2.79, 3.15-3.56, 4.03-4.18, 4.44-4.54, 5.16-5.28, 7.32-7.55. Some signals overlap with solvent. HRMS (M+H)+: calculated 283.1213. found 283.1219.

Workup

  1. temperaturewas cooled on an ice-bath
  2. customThe ice-bath was removed
  3. stirringthe reaction was stirred at rt over night
  4. additionDCM (3 mL) was added
  5. washthe mixture was washed with NaHCO3 (8% aq., 3 mL)
  6. filtrationfiltered through a phase separator
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in MeOH (2 mL)
  9. additionNaOH (aq., 2M) was added
  10. stirringThe resulting mixture was stirred at rt for 3 h
  11. concentrationconcentrated under reduced pressure
  12. additionDCM (5 mL) and NaHCO3, (aq., 8%, 5 mL) was added
  13. customThe organic phase was collected
  14. customthe solvents were removed under reduced pressure
  15. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-3c03ca24c4df4e7da9a80f25029dd98b
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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