Thionyl Chloride → HCID 67415262, compound

HRID 1916970Notes

Reaction equation

HRID 1916970 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([C:6]([C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[C:10]([OH:12])=O)=[O:7])=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[Cl:23][C:24]1[CH:32]=[CH:31][C:27]([C@@H:28]([NH2:30])[CH3:29])=[CH:26][CH:25]=1.CCN(C(C)C)C(C)C>C1COCC1.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]2([OH:7])[C:8]3[C:9](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:10](=[O:12])[N:30]2[CH:28]([C:27]2[CH:31]=[CH:32][C:24]([Cl:23])=[CH:25][CH:26]=2)[CH3:29])=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 665642-(4'-Chlorobenzoyl)benzoic acidHCID 81531DiisopropylethylamineHCID 1550852(S)-(-)-1-(4-chlorophenyl)ethylamine

Product 1

HCID 67415262HCID 67415262, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(4-chlorobenzoyl)benzoic acid (5 g, 19.2 mmol, 1 equiv.) in dry THF (20 mL) was added under nitrogen atmosphere thionylchloride (3.0 mL, 38.3 mmol, 2 equiv.) and 3 drops of anhydrous DMF. The reaction mixture was stirred for 4 h at room temperature and concentrated in vacuo. The resulting pale yellow oil was taken up in dry THF (20 mL), and (S)-4-chloro-α-methylbenzylamine (2.43 g, 15.6 mmol, 1.1 equiv.) and DIPEA (3.49 mL, 21.1 mmol, 1.1 equiv.) were added under nitrogen atmosphere. The reaction mixture was stirred overnight at room temperature and the solvents were removed in vacuo. The residue was taken up in EtOAc (100 mL), filtered, and the filtrate washed with water (3×50 mL) and brine (1×50 mL). The organic layer was dried over MgSO4, filtered and concentrated in vacuo to afford a solid, which was recrystallised (EtOAc/Petrol) as a white crystalline powder (3.10 g, 55%). 1H NMR (300 MHz, CDCl3): Mixture of two diastereoisomers: 7.74-7.09 (m, 13H, Ar—H and OH), 4.52 and 4.45 (q, J=6.9 Hz, 1H, CH*), 1.75 and 1.48 (d, J=7.2 Hz, 3H, CH3). 13C NMR (75 MHz, CDCl3): Mixture of two diastereoisomers: 166.94, 166.43, 149.17, 149.11, 142.01, 141.51, 139.65, 139.33, 133.24, 133.14, 132.90, 131.76, 131.60, 131.54, 131.47, 129.79, 129.71, 129.52, 128.67, 128.62, 128.26, 127.88, 127.84, 123.13, 122.74, 122.70, 91.19, 90.94, 51.22, 50.46, 20.21, 18.24. FTIR: 3103 (OH), 1665 (C═O) cm−1. m/z (ES): 398 [M+H]+. Anal.: calc. for C22H17Cl2NO2+0.3 H2O: C, 65.45; H, 4.40; N, 3.47. Found: C, 65.00; H, 4.30; N, 3.60.

Workup

  1. concentrationconcentrated in vacuo
  2. stirringThe reaction mixture was stirred overnight at room temperature
  3. customthe solvents were removed in vacuo
  4. filtrationfiltered
  5. washthe filtrate washed with water (3×50 mL) and brine (1×50 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a solid, which
  10. customwas recrystallised (EtOAc/Petrol) as a white crystalline powder (3.10 g, 55%)

Sources & evidence

ORD record
ord-c56a5221506a48fd8ab10230cf22103a
Source dataset
uspto-grants-2013_12
Patent number
US08618158B2

Reaction notes

Loading…