Triethylamine → tert-Butyl 3-((3,5-dichloro-N-((4'-fluorobiphenyl-4-yl)methyl)-2-hydroxyphenylsulfonamido)methyl)benzylcarbamate

HRID 1889678Notes

Reaction equation

HRID 1889678 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][NH:15][CH2:16][C:17]3[CH:18]=[C:19]([CH:29]=[CH:30][CH:31]=3)[CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[Cl:39][C:40]1[C:41]([OH:51])=[C:42]([S:47](Cl)(=[O:49])=[O:48])[CH:43]=[C:44]([Cl:46])[CH:45]=1>ClCCl>[Cl:39][C:40]1[C:41]([OH:51])=[C:42]([S:47]([N:15]([CH2:16][C:17]2[CH:18]=[C:19]([CH:29]=[CH:30][CH:31]=2)[CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[CH2:14][C:11]2[CH:10]=[CH:9][C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[CH:13][CH:12]=2)(=[O:49])=[O:48])[CH:43]=[C:44]([Cl:46])[CH:45]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 900783,5-Dichloro-2-hydroxybenzenesulphonyl chlorideHCID 58531402tert-Butyl 3-(((4'-fluorobiphenyl-4-yl)methylamino)methyl)benzylcarbamate

Product 1

HCID 58531334tert-Butyl 3-((3,5-dichloro-N-((4'-fluorobiphenyl-4-yl)methyl)-2-hydroxyphenylsulfonamido)methyl)benzylcarbamateYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

tert-Butyl 3-(((4′-fluorobiphenyl-4-yl)methylamino)methyl)benzylcarbamate (1.8 g, 4.28 mmol, 1.0 eq) was dissolved in dichloromethane and cooled 0° C. Triethylamine (1.85 mL, 12.8 mmol, 3.0 eq) was added slowly over 5-10 minutes and the mixture was stirred for 10 minutes at 0° C. 3,5-Dichloro-2-hydroxybenzene-1-sulfonyl chloride (1.2 g, 4.7 mmol, 1.1 eq) was dissolved in DCM and added slowly to the above mixture at 0° C. After 2 h, the reaction mixture was concentrated under vacuum at low temperature and the white precipitate that formed was removed. The solution was purified by silica gel (60-120) column chromatography using 15-20% ethyl acetate/hexane as the eluent to afford the desired product (2.3 g, 85%). 1H NMR (400 MHz, CD3OD) δ 1.45 (d, 9H), 4.11-4.15 (d, 2H) 4.49-4.52 (d, 4H), 7.07-7.19 (m, 8H), 7.42-7.44 (d, 2H), 7.56-7.59 (m, 3H), 7.65-7.66 (d, 1H). MS (ESI): 644.0 (M−H)−.

Workup

  1. additionadded slowly to the above mixture at 0° C
  2. waitAfter 2 h
  3. concentrationthe reaction mixture was concentrated under vacuum at low temperature
  4. customthe white precipitate that formed
  5. customwas removed
  6. customThe solution was purified by silica gel (60-120) column chromatography

Sources & evidence

ORD record
ord-15e31f7d6c1d4489bc7f5a4d54ed3874
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

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