Sodium hydride → (5-{3-[4-(4-Chloro-phenyl)-4-hydroxy-3-methyl-piperidin-1-yl]-propylidene}-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yloxy)-acetic acid methyl ester

HRID 457144Notes

Reaction equation

HRID 457144 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:34])[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][CH:9]2[CH3:33])=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:38][C:39]([O:41][CH3:42])=[O:40]>CN(C)C=O>[CH3:42][O:41][C:39](=[O:40])[CH2:38][O:32][C:30]1[CH:29]=[CH:28][C:19]2[O:20][CH2:21][C:22]3[N:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:17](=[CH:16][CH2:15][CH2:14][N:11]3[CH2:12][CH2:13][C:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)([OH:34])[CH:9]([CH3:33])[CH2:10]3)[C:18]=2[CH:31]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 536307665-{3-[4-(4-Chloro-phenyl)-4-hydroxy-3-methyl-piperidin-1-yl]-propylidene}-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-ol

Product 1

HCID 66758361(5-{3-[4-(4-Chloro-phenyl)-4-hydroxy-3-methyl-piperidin-1-yl]-propylidene}-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yloxy)-acetic acid methyl esterYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-{3-[4-(4-Chloro-phenyl)-4-hydroxy-3-methyl-piperidin-1-yl]-propylidene}-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-ol (0.14 g, 0.28 mmol) in dimethylformamide (3 mL) was treated with sodium hydride (60% in mineral oil, 0.016 g, 0.4 mmol) and methyl bromoacetate (0.038 mL, 0.4 mmol). The mixture was allowed to stir at rt for 2 hr, then quenched with aqueous brine, and extracted with ethyl acetate (3×10 mL). The combined organics were washed several time with water, dried over sodium sulfate, and evaporated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate→487:10:3 ethyl acetate/methanol/triethylamine) to yield 0.07 g (50%) of the title compound, ESI-MS m/z: 549 [M+1].

Workup

  1. customquenched with aqueous brine
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. washThe combined organics were washed several time with water
  4. dry with materialdried over sodium sulfate
  5. customevaporated in vacuo
  6. customThe residue was purified by silica gel chromatography (ethyl acetate→487:10:3 ethyl acetate/methanol/triethylamine)

Sources & evidence

ORD record
ord-8a1334eb93114711961ed3f63be445d4
Source dataset
uspto-grants-2007_03
Patent number
US07186729B2

Reaction notes

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