Sodium Hydroxide → HCID 9917169, compound

HRID 1954260Notes

Reaction equation

HRID 1954260 reaction equation
[Br:1][C:2]1[C:11]2[S:12][C:13]([CH3:16])=[C:14]([CH3:15])[C:10]=2[C:9]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[C:19]([CH:24]([CH3:26])[CH3:25])[CH:18]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[CH:7]2.[OH-].[Na+].Cl[S:30]([C:33]1[CH:41]=[CH:40][C:36]([C:37]([OH:39])=[O:38])=[C:35]([OH:42])[CH:34]=1)(=[O:32])=[O:31]>C(O)C(N)(CO)CO.C1COCC1>[Br:1][C:2]1[C:11]2[S:12][C:13]([CH3:16])=[C:14]([CH3:15])[C:10]=2[C:9]([C:17]2[CH:22]=[CH:21][C:20]([O:23][S:30]([C:33]3[CH:41]=[CH:40][C:36]([C:37]([OH:39])=[O:38])=[C:35]([OH:42])[CH:34]=3)(=[O:32])=[O:31])=[C:19]([CH:24]([CH3:26])[CH3:25])[CH:18]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[CH:7]2

Participants

6

Reactant 3

HCID 14798Sodium Hydroxide2×HCID 146685314-(Chlorosulfonyl)-2-hydroxybenzoic acid2×HCID 15490891HCID 15490891, compound

Product 1

HCID 9917169HCID 9917169, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 6503Tris(hydroxymethyl)aminomethaneSolventHCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
5 °C

Procedure

At ambient temperature, to a stirred suspension of 4-(9-bromo-2,3-dimethyl-naphtho[2,3-b]thiophen-4-yl)-2-isopropyl-phenol (0.306 g, 0.744 mmol) in 0.05 M Tris buffer pH 9: THF (10:3, 3.56 mL, 0.2 M) was added 2.5N NaOH (0.285 mL, 0.713 mmol) followed by a minimal amount of THF to form a solution. After 0.5 h, the reaction was cooled to 5° C. To the reaction was added dropwise, a solution of 4-chlorosulphonyl-2-hydroxybenzoic acid (0.338 g, 1.43 mmol) in THF (2.85 mL, 0.5M) while maintaining the pH at 10 with the simultaneous addition of 2N NaOH. After the addition was completed, the reaction was allowed to warm to ambient temperature and stirred for 1.5 h. At 5° C. additional 4-chlorosulphonyl-2-hydroxybenzoic acid (0.338 g, 1.43 mmol) in THF (2.85 mL, 0.5 M) was added in the exact same manner as above and the reaction was stirred for 1.5 h. The reaction was quenched with 2N HCl (40 mL) and extracted with EtOAc. The combined organic extracts were washed with 2N HCl (3×), dried (MgSO4) and concentrated. Purification on 2% H3PO4 /MeOH treated Biotage KP-Sil eluting with a 15 & 25% EtOAc/Hexane step gradient gave 0.294 g, (66%) of the title compound as a yellow solid, mp >225° C.; 1H NMR (DMSO-d6): δ 0.96 (d, 3 H), 1.02 (d, 3 H), 1.48 (s, 3 H), 2.50 (s, 3 H), 3.08 (heptet, 1 H), 7.26-7.39 (m, 5 H), 7.43 (dd, 1 H), 7.50 (t, 1 H), 7.66 (t, 1 H), 8.05 (d, 1 H), 8.21 (d, 1 H). IR (KBr) 3425, 2950, 1675, 1400 and 1190 cm-1. mass spectrum (-ESI), m/z 623/625 (M-H). Anal. Calcd. for C30H25BrO6S2 : C, 57.60; H, 4.03; N, 0.00. Found: C, 57.88; H, 4.29 N, 0.09.

Workup

  1. customto form a solution
  2. additionTo the reaction was added dropwise
  3. additionAfter the addition
  4. temperatureto warm to ambient temperature
  5. stirringwas stirred for 1.5 h
  6. customThe reaction was quenched with 2N HCl (40 mL)
  7. extractionextracted with EtOAc
  8. washThe combined organic extracts were washed with 2N HCl (3×)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customPurification on 2% H3PO4 /MeOH treated Biotage KP-Sil
  12. washeluting with a 15 & 25% EtOAc/Hexane step gradient

Sources & evidence

ORD record
ord-eeeb209b34fb49b7a9a6f386de349a1d
Source dataset
uspto-grants-2000_09
Patent number
US06121271

Reaction notes

Loading…