Sodium Hydroxide → 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl]-pentanoic Acid

HRID 2106237Notes

Reaction equation

HRID 2106237 reaction equation
C[O:2][C:3](=[O:25])[CH2:4][CH2:5][CH2:6][CH2:7][N:8]1[C:17]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[C:16]2[C:10]([CH2:11][CH2:12][NH:13][CH2:14][CH2:15]2)=[N:9]1.[OH-].[Na+]>C1COCC1.CO>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([C:17]2[N:8]([CH2:7][CH2:6][CH2:5][CH2:4][C:3]([OH:25])=[O:2])[N:9]=[C:10]3[C:16]=2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)=[CH:19][CH:20]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 24872786HCID 24872786, compound

Product 1

HCID 248727885-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl]-pentanoic AcidYield 23.1%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl]-pentanoic acid methyl ester (Example 82, 0.009 g) was dissolved in 1 mL of 9:1 THF/MeOH and treated with 2 mL of 1 M NaOH. After stirring at RT for 5 h, the solvent was removed in vacuo. The aqueous residue was acidified with 1 mL of 1 N HCl and the mixture was extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, concentrated, and dried on a vacuum line. The residue was then dissolved in 1 mL of 9:1 CH2Cl2/MeOH and treated with 3 mL of 1 N HCl in Et2O. After 4 h, the volatiles were removed in vacuo. The crude oil was purified by preparative TLC (9:1 CH2Cl2/2 M NH3 in MeOH) to afford 0.002 g of the title compound. MS (ESI): exact mass calculated for C18H22ClN3O2, 347.14; found, m/z 348.1 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.55-7.53 (m, 4H), 7.35-7.32 (m, 2H), 3.98 (t, J=7.0 Hz, 2H), 3.38-3.35 (m, 2H), 3.28-3.26 (m, 2H), 3.13-3.10 (m, 2H), 2.77-2.74 (m, 2H), 2.09-2.06 (m, 2H), 1.71-1.66 (m, 2H), 1.41-1.37 (m, 2H).

Workup

  1. customthe solvent was removed in vacuo
  2. extractionthe mixture was extracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. concentrationconcentrated
  5. customdried on a vacuum line
  6. dissolutionThe residue was then dissolved in 1 mL of 9:1 CH2Cl2/MeOH
  7. additiontreated with 3 mL of 1 N HCl in Et2O
  8. waitAfter 4 h
  9. customthe volatiles were removed in vacuo
  10. customThe crude oil was purified by preparative TLC (9:1 CH2Cl2/2 M NH3 in MeOH)

Sources & evidence

ORD record
ord-f92d99906001407e961f3b2a165fff6e
Source dataset
uspto-grants-2009_08
Patent number
US07579470B2

Reaction notes

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