Sodium Hydroxide → HCID 18518250, compound

HRID 1369237Notes

Reaction equation

HRID 1369237 reaction equation
[OH-].[Na+].[CH2:3]([O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([NH:12][CH2:13][CH2:14][CH2:15][O:16][C:17]2[CH:18]=[CH:19][C:20]3[CH2:26][CH:25]([CH2:27][C:28]([O:30]CC)=[O:29])[C:24]4[CH:33]=[CH:34][CH:35]=[CH:36][C:23]=4[CH2:22][C:21]=3[CH:37]=2)[CH:7]=1)[CH3:4]>C(O)C>[CH2:3]([O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([NH:12][CH2:13][CH2:14][CH2:15][O:16][C:17]2[CH:18]=[CH:19][C:20]3[CH2:26][CH:25]([CH2:27][C:28]([OH:30])=[O:29])[C:24]4[CH:33]=[CH:34][CH:35]=[CH:36][C:23]=4[CH2:22][C:21]=3[CH:37]=2)[CH:7]=1)[CH3:4]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 20592630HCID 20592630, compound

Product 1

HCID 18518250HCID 18518250, compoundYield 91.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
45 °C

Procedure

1.0 N NaOH (1.7 mL, 1.7 mmole) was added dropwise to a solution of ethyl (±)-10,11-dihydro-3-[3-(4-ethoxypyridin-2-ylamino)-1-propyloxy]-5H-dibenzo[a,d]cycloheptene-10-acetate (528.1 mg, 1.11 mmole) in absolute ethanol (11 mL) at RT, and the solution was warmed in an oil bath preset at 45° C. After 20 hr, the reaction was concentrated, and the residue was reconcentrated from H2O. The resulting residue was dissolved in H2O (10 mL) and the solution was filtered. The pH was adjusted to 7 with 1.0 N HCl, and the mixture was stirred briskly to convert the initially-formed gummy precipitate into a solid. Trituration with a glass rod and a spatula aided in this transformation. The pH of the resulting mixture was readjusted to 7, and the solid was collected and washed with plenty of H2O. The filtrate was concentrated and the residue was dissolved in H2O with the aid of a little 1.0 N NaOH. The pH was adjusted to 7 to afford a small second crop. The crops were combined and dried in vacuum (40-50° C.) to afford the title compound (453.7 mg, 82%) as an off-white solid: HPLC (Hamilton PRP-1®, 45% CH3CN/H2O containing 0.1% TFA) k′=1.32; 1H NMR (400 MHz, DMSO-d6) δ7.78 (d, J=6.6 Hz, 1 H), 7.35-7.65 (m, 1 H), 7.02-7.22 (m, 4 H), 6.97 (d, J=8.3 Hz, 1 H), 6.82 (d, J=2.4 Hz, 1 H), 6.68 (dd, J=8.3, 2.4 Hz, 1 H), 6.29 (dd, 1 H), 6.15 (narrow d, 1 H), 4.20 (d, J=14.6 Hz, 1 H), 3.93-4.12 (m, 4 H), 3.89 (d, J=14.6 Hz, 1 H), 3.60-3.71 (m, 1 H), 3.30-3.50 (m, 2 H), 3.20 (dd, J=15.1, 4.1 Hz, 1 H), 2.83 (dd, J=15.1, 10.1 Hz, 1 H), 2.60 (dd, J=16.0, 5.3 Hz, 1 H), 2.48 (dd, J=16.0, 8.9 Hz, 1 H, partially obscured by residual solvent signal), 1.90-2.05 (m, 2 H), 1.30 (t, J=6.9 Hz, 3 H); MS (ES) m/e 447 (M+H)+. Anal. Calcd for C27H30N2O4.1.5 HCl: C, 64.70; H, 6.33; N, 5.59. Found: C, 64.53; H, 6.14; N, 5.31.

Workup

  1. concentrationthe reaction was concentrated
  2. dissolutionThe resulting residue was dissolved in H2O (10 mL)
  3. filtrationthe solution was filtered
  4. customthe solid was collected
  5. washwashed with plenty of H2O
  6. concentrationThe filtrate was concentrated
  7. dissolutionthe residue was dissolved in H2O with the aid of a little 1.0 N NaOH
  8. customto afford a small second crop
  9. customdried in vacuum (40-50° C.)

Sources & evidence

ORD record
ord-0156938e3ccd4483b103320029ecb1f3
Source dataset
uspto-grants-2003_06
Patent number
US06576643B2

Reaction notes

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