Methanol → HCID 24965128, compound

HRID 506544Notes

Reaction equation

HRID 506544 reaction equation
[NH:1]1[CH2:6][CH2:5][C:4]2([CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:8]3[CH:14]=[CH:15][CH:16]=[CH:17][C:7]2=3)[CH2:3][CH2:2]1.[C:18]1(=O)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CO>ClCCCl.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[CH:18]1([N:1]2[CH2:6][CH2:5][C:4]3([CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:8]4[CH:14]=[CH:15][CH:16]=[CH:17][C:7]3=4)[CH2:3][CH2:2]2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

7

Reactant 4

HCID 887MethanolHCID 10400CycloheptanoneHCID 5049666Sodium triacetoxyborohydrideHCID 59432280HCID 59432280, compound

Product 1

HCID 24965128HCID 24965128, compound

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 3,4-dihydrospiro[benzo[b]azepine-5,4′-piperidin]-2(1H)-one E (800 mg, 3.47 mmol) and cycloheptanone (1.12 g, 10 mmol) in 1,2-dichloroethane (25 ml) was added titanium tetraisopropoxide (2.5 ml, 8.8 mmol) and the resulting solution was stirred at 40° C. for 15 h, treated with sodium triacetoxyborohydride (2.12 g, 10 mmol) for 1 h, cooled to room temperature and MeOH (1 ml) was added and stirred for 1 h. After evaporation, the residue was dissolved in dichloromethane, washed with a mixture of brine and 6N NaOH (3 ml). The aqueous phase (suspension) was extracted with dichloromethane (3×). The extracts were dried over Na2SO4, concentrated and purified by silica gel chromatography (CH2Cl2/MeOH 9:1 to 8:2) to give 1′-cycloheptyl-3,4-dihydrospiro[benzo[b]azepine-5,4′-piperidin]-2(1H)-one (800 mg). LC-MS: m/e=327.1 (M+H, 100%). Rt=1.57 min. 1H-NMR (500 MHz, DMSO (d6)): 9.46 (s, 1H), 7.37 (d, 1H), 7.20 (t, 1H), 7.12 (t, 1H), 6.95 (d, 1H), 2.51 (m, 2H), 2.44-2.35 (m, 3H), 2.08 (t, 2H), 2.01 (t, 2H), 1.94 (m, 2H), 1.86 (m, 2H), 1.66 (m, 2H), 1.58 (m, 2H), 1.49-1.39 (m, 6H), 1.35-1.29 (m, 2H). The above product was suspended in water, filtration and the solid was dissolved in a diluted 1N HCl (6 ml), lyophilized to give a HCl salt 24 (723 mg). Two conformers were observed with ca. 1:2 ratios. 1H-NMR (500 MHz, DMSO-d6): 10.03 (m, 1H); 9.61, 9.57 (2s, 1H); 7.42 (d, 0.35H), 7.38 (d, 0.65H); 7.31, 7.26 (2t, 1H); 7.21, 7.16 (2t, 1H); 7.05, 7.01 (2t, 1H); 3.29 (d, 2H), 3.21 (q, 2H), 2.73 (d, 0.7H), 2.28 (d, 1.3H), 2.63-2.57 (m, 1H), 2.22-1.98 (m, 8H), 1.89-1.84 (m, 1H), 1.73-1.60 (m, 3H), 1.55-1.33 (m, 7H).

Workup

  1. temperaturecooled to room temperature
  2. stirringstirred for 1 h
  3. customAfter evaporation
  4. dissolutionthe residue was dissolved in dichloromethane
  5. washwashed with a mixture of brine and 6N NaOH (3 ml)
  6. extractionThe aqueous phase (suspension) was extracted with dichloromethane (3×)
  7. dry with materialThe extracts were dried over Na2SO4
  8. concentrationconcentrated
  9. custompurified by silica gel chromatography (CH2Cl2/MeOH 9:1 to 8:2)

Sources & evidence

ORD record
ord-afe1604577394ebdb38b5944137981bb
Source dataset
uspto-grants-2010_08
Patent number
US07786107B2

Reaction notes

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