4-Chlorobenzoic Acid → HCID 67773688, compound

HRID 1808847Notes

Reaction equation

HRID 1808847 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)C(C)C)C.[CH:42]([NH:45][C@@H:46]([CH2:53][CH2:54][CH3:55])[CH2:47][N:48]1[CH2:51][CH:50]([OH:52])[CH2:49]1)([CH3:44])[CH3:43]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:45]([C@@H:46]([CH2:53][CH2:54][CH3:55])[CH2:47][N:48]2[CH2:51][CH:50]([OH:52])[CH2:49]2)[CH:42]([CH3:44])[CH3:43])=[O:8])=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 63184-Chlorobenzoic AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67772642HCID 67772642, compound

Product 1

HCID 67773688HCID 67773688, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 4-chlorobenzoic acid (0.067 g, 0.43 mmol) and TBTU (0.137 g, 0.43 mmol) in DCM (2 mL) was added N-ethyl-N-isopropylpropan-2-amine (0.222 mL, 1.28 mmol). The suspension was stirred at rt for 30 min. A solution of (S)-1-(2-(isopropylamino)pentyl)azetidin-3-ol (Compound O2.1) (0.142 g, 0.43 mmol) in DCM (1 mL) was added and the reaction mixture was stirred at rt overnight. The reaction was washed with saturated NaHCO3 solution (2 ml). The organic phase was concentrated using a vacuum centrifuge. The residue was dissolved in MeOH (2 ml) and 1M NaOH (aq., 0.5 ml) was added. The mixture was stirred at rt for 1.5 h. Acetic acid (110 mg) was added and the mixture was concentrated. The residue was dissolved in DCM (3.5 ml) and washed with saturated NaHCO3 solution (2 ml). The organic phase was concentrated using a vacuum centrifuge and the residue purified by preparative HPLC affording the title compound (20 mg, 14%). Mixture of rotamers: 1H NMR (600 MHz, DMSO-d6) δ 0.62-0.78, 0.76-0.93, 0.93-1.14, 1.14-1.54, 1.67-1.93, 2.24-2.40, 2.41-2.77, 2.76-2.97, 2.96-3.15, 3.16-3.45, 3.45-3.75, 3.96-4.20, 5.12-5.31, 7.17-7.35, 7.38-7.52. Number of protons: 27. HRMS (M+H)+: calculated 339.1839. found 339.1866

Workup

  1. stirringthe reaction mixture was stirred at rt overnight
  2. washThe reaction was washed with saturated NaHCO3 solution (2 ml)
  3. concentrationThe organic phase was concentrated
  4. dissolutionThe residue was dissolved in MeOH (2 ml)
  5. addition1M NaOH (aq., 0.5 ml) was added
  6. stirringThe mixture was stirred at rt for 1.5 h
  7. additionAcetic acid (110 mg) was added
  8. concentrationthe mixture was concentrated
  9. dissolutionThe residue was dissolved in DCM (3.5 ml)
  10. washwashed with saturated NaHCO3 solution (2 ml)
  11. concentrationThe organic phase was concentrated
  12. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-5d8098d15c1b4023b462b9c25f7c7e24
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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