Tetrahydrofuran → HCID 9875187, compound

HRID 1743499Notes

Reaction equation

HRID 1743499 reaction equation
[CH2:1]([NH:13][C:14](=[O:33])[C:15]1[CH:20]=[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=2)[C:18]([OH:31])=[C:17]([Br:32])[CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C1COCC1.[OH-].[Na+].Cl[S:42]([C:45]1[CH:53]=[CH:52][C:48]([C:49]([OH:51])=[O:50])=[C:47]([OH:54])[CH:46]=1)(=[O:44])=[O:43]>C(O)C(N)(CO)CO>[Br:32][C:17]1[C:18]([O:31][S:42]([C:45]2[CH:53]=[CH:52][C:48]([C:49]([OH:51])=[O:50])=[C:47]([OH:54])[CH:46]=2)(=[O:44])=[O:43])=[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=2)[CH:20]=[C:15]([C:14](=[O:33])[NH:13][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH:16]=1

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 14798Sodium Hydroxide2×HCID 146685314-(Chlorosulfonyl)-2-hydroxybenzoic acidHCID 22237479HCID 22237479, compound

Product 1

HCID 9875187HCID 9875187, compoundYield 81.3%

Reagents, catalysts & solvents 1

HCID 6503Tris(hydroxymethyl)aminomethaneSolvent

Procedure

To a suspension of N-dodecyl-3-bromo-4-hydroxy-5-(m-trifluoromethylphenyl)-benzamide (1.799 g, 1.51 mmol, 1 eq) in 0.05 N tris(hydroxymethyl)aminomethane pH 9 buffer/THF (10:3) (7.5 mL) was added 2.5 N NaOH (0.665 mL, 1.66 mmol, 1.1 eq) and THF (10 mL). The reaction was stirred at rt for 30 minutes and then cooled to 5° C. 4-Chlorosulfonyl-2-hydroxy-benzoic acid (0.715 g, 3.02 mmol, 2 eq) was added portionwise while keeping the pH at 9 by the addition of 2.5 N NaOH. This mixture was allowed to warm to rt and to stir for 2 days. The reaction was quenched by the addition of 2 M HCl solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (30% EtOAc:hexane+1% Formic Acid) to afford the title compound (0.895 g, 79%) as a yellow foam. 1H NMR (DMSO-d6) δ 11.40 (bs, 1H); 10.35 (bs, 1H); 8.70 (t, 1H); 8.22 (d, 1H); 7.85 (d, 1H); 7.72–7.45 (m, 5H); 6.98 (dd, 1H); 6.86 (d, 1H); 3.25 (dd, 2H); 1.50 (dd, 2H); 1.25 (m, 18H); 0.85 (t, 3H); IR (KBr) 3410, 2800, 2700, 1690, 1640, 1605, 1390, 1330, 1180, 1120, 620, 600 cm1; mass spectrum [(+)APCI], m/z 728/730 (M+H)+; Anal. Calcd. for C33H37BrF3NO7S+0.25 C4H8O2: C, 54.40; H, 5.24; N, 1.87. Found: C, 53.23; H, 4.77; N, 1.79.

Workup

  1. temperaturecooled to 5° C
  2. temperatureto warm to rt
  3. stirringto stir for 2 days
  4. customThe reaction was quenched by the addition of 2 M HCl solution
  5. extractionextracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography (30% EtOAc:hexane+1% Formic Acid)

Sources & evidence

ORD record
ord-eaea7b243a344156a52e8560ca1559d3
Source dataset
uspto-grants-2006_03
Patent number
US07008636B2

Reaction notes

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