Triethylamine → HCID 66616471, compound

HRID 1889690Notes

Reaction equation

HRID 1889690 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([S:12](Cl)(=[O:14])=[O:13])[C:10]=1[OH:11])[C:5]([OH:7])=O.C([N:18]([CH2:21][CH3:22])CC)C.[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([CH2:36][NH:37][CH2:38][C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=3)[CH:31]=2)=[CH:26][CH:25]=1>ClCCl>[CH2:21]([NH:18][C:5](=[O:7])[C:4]1[CH:8]=[C:9]([S:12](=[O:14])(=[O:13])[N:37]([CH2:36][C:32]2[CH:31]=[C:30]([C:27]3[CH:28]=[CH:29][C:24]([Cl:23])=[CH:25][CH:26]=3)[CH:35]=[CH:34][CH:33]=2)[CH2:38][C:39]2[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=2)[C:10]([OH:11])=[C:2]([Cl:1])[CH:3]=1)[C:22]1[CH:4]=[CH:3][CH:2]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 545935123-Chloro-5-(chlorosulfonyl)-4-hydroxybenzoic acid2×HCID 58531372HCID 58531372, compound

Product 1

HCID 66616471HCID 66616471, compoundYield 43.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a heterogeneous mixture of 3-chloro-5-(chlorosulfonyl)-4-hydroxybenzoic acid (0.47 g, 1.8 mmol) in anhydrous dichloromethane (20 mL), at room temperature under nitrogen, was added triethylamine (0.49 mL, 3.5 mmol). To the resulting homogeneous mixture was added a solution of 1-(4′-chlorobiphenyl-3-yl)-N-(4-fluoro-benzyl)methanamine (1.1 g, 3.5 mmol) in anhydrous DCM (5 mL). The resulting mixture was stirred for 15 h before 3-chloro-5-(chlorosulfonyl)-4-hydroxybenzoic acid (0.47 g, 1.8 mmol) was added. After 3.5 h, triethylamine (0.49 mL, 3.5 mmol) was added and the reaction mixture was war wed to 40° C. After 6 h, the reaction mixture was concentrated in vacuo to remove volatiles and treated with saturated aqueous NaHCO3 solution. The resulting mixture was washed twice with Et2O and the organic washings were discarded. The aqueous layer was acidified with 1 N HCl until pH 1-2 (EMD color PHast pH 0-14 pH strips) and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford an off-white solid. The crude product was purified by preparative HPLC (YMC-Pack, ODS-A, 50×500 mm, 30 minute gradient from 50% to 90% aqueous methanol with 0.1% TFA) to afford the desired compound (254 mg, 26%) as a white solid. 1H NMR (DMSO-d6) δ 13.25 (bs, 1H), 8.20 (d, J=2.0 Hz, 1H), 8.02 (d, J=2.0 Hz, 1H), 7.57-7.46 (m, 5H), 7.38-7.05 (m, 7H), 4.54 (s, 2H), 4.50 (s, 2H). MS (ESI): 558.2 (M−H)−.

Workup

  1. additionwas added
  2. customwed to 40° C
  3. waitAfter 6 h
  4. concentrationthe reaction mixture was concentrated in vacuo
  5. customto remove volatiles
  6. additiontreated with saturated aqueous NaHCO3 solution
  7. washThe resulting mixture was washed twice with Et2O
  8. extractionextracted three times with ethyl acetate
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto afford an off-white solid
  14. customThe crude product was purified by preparative HPLC (YMC-Pack, ODS-A, 50×500 mm, 30 minute gradient from 50% to 90% aqueous methanol with 0.1% TFA)

Sources & evidence

ORD record
ord-adcf3cbc912e4fb9a2dcc4c03109dbba
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

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