Triethylamine → HCID 66616471、化合物

HRID 1889690ノート

反応式

HRID 1889690 の反応式
[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

参加物

5

反応物 3

HCID 8471Triethylamine2 回HCID 545935123-Chloro-5-(chlorosulfonyl)-4-hydroxybenzoic acid2 回HCID 58531372HCID 58531372、化合物

生成物 1

HCID 66616471HCID 66616471、化合物収率 43.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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)−.

後処理

  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)

出典と根拠

ORDレコード
ord-adcf3cbc912e4fb9a2dcc4c03109dbba
出典データセット
uspto-grants-2013_08
特許番号
US08501992B2

反応ノート

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