Sodium hydride → HCID 66759153, compound

HRID 917233Notes

Reaction equation

HRID 917233 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:35])[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH:16]=[C:17]3[C:23]4[CH:24]=[CH:25][CH:26]=[N:27][C:22]=4[CH2:21][O:20][C:19]4[CH:28]=[CH:29][C:30]([OH:32])=[CH:31][C:18]3=4)[CH2:10][C:9]2([CH3:34])[CH3:33])=[CH:4][CH:3]=1.[H-].[Na+].Cl.Cl[CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:35])[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH:16]=[C:17]3[C:23]4[CH:24]=[CH:25][CH:26]=[N:27][C:22]=4[CH2:21][O:20][C:19]4[CH:28]=[CH:29][C:30]([O:32][CH2:40][CH2:41][N:42]5[CH2:47][CH2:46][O:45][CH2:44][CH2:43]5)=[CH:31][C:18]3=4)[CH2:10][C:9]2([CH3:33])[CH3:34])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 66757704HCID 66757704, compound

Product 1

HCID 66759153HCID 66759153, compoundYield 29.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-{3-[4-(4-chloro-phenyl)-4-hydroxy-3,3-dimethyl-piperidin-1-yl]-propylidene}-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-ol (0.15 g, 0.28 mmol) in DMF (1.5 mL) was added NaH (0.034 g, 0.84 mmol) and stirred for 20 min. at room temperature. 4-(2-Chloro-ethyl)-morpholine HCl (0.063 g, 0.34 mmol) was added and the solution was heated to 50° C. for 16 h. The reaction was quenched with water and extracted with ethyl acetate (3×). The organics were combined, dried over Mg2SO4, filtered and concentrated, then purified by Biotage flash chromatography (5–10% methanol/dichloromethane) to yield the title compound (0.050 g). 1H-NMR (MeOD) δ: 0.73 (3H, s), 0.85 (3H, s), 2.39–2.90 (11H, m), 3.29–3.31 (3H, m), 3.69–3.72 (4H, m), 4.1 (2H, t), 5.20 (2H, br s), 6.18 (1H, t), 6.74–6.79 (2H, m), 6.89 (1H, d), 7.27–7.30 (2H, m), 7.43–7.47 (3H, m), 7.79 (1H, dd), 8.46 (1H, dd). ESI-MS m/z: 604 (M), UV retention time: 1.20 min.

Workup

  1. temperaturethe solution was heated to 50° C. for 16 h
  2. customThe reaction was quenched with water
  3. extractionextracted with ethyl acetate (3×)
  4. dry with materialdried over Mg2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by Biotage flash chromatography (5–10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-df5885b7cd1d45ffbbe71cef1e046773
Source dataset
uspto-grants-2007_09
Patent number
US07271176B2

Reaction notes

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