Lithium Hydroxide → HCID 66868768, compound

HRID 84589Notes

Reaction equation

HRID 84589 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[C:20](C(O)=O)=[N:19][C:18]2[C:17]3[S:24][C:25](CC)=[CH:26][C:16]=3[CH2:15][CH2:14][O:13][C:12]=2[CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[O:29]1[CH2:33]CCC1.[OH-:34].[Li+]>O>[Si:1]([O:8][CH2:9][C:10]1[CH:20]=[N:19][C:18]2[C:17]3[S:24][C:25]([C:33]([OH:29])=[O:34])=[CH:26][C:16]=3[CH2:15][CH2:14][O:13][C:12]=2[CH:11]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 131728794HCID 131728794, compound

Product 1

HCID 66868768HCID 66868768, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To a solution of 3-tert-butyldimethylsilyloxymethyl-9-ethylcarboxy-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepine (0.100 g, 0.238 mmol) in tetrahydrofuran (0.715 mL, 8.82 mmol) and water (0.715 mL, 39.7 mmol) was added 1.00 M of lithium hydroxide in water (0.715 mL). The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated and the residue was acidified with 1M HCl then extracted with EtOAc (3×). The combined organics were dried (Na2SO4), filtered and concentrated to give 3-tert-butyldimethylsilyloxymethyl-9-carboxy-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepine to which was added 5 ml DCM, triethylamine (0.166 mL, 1.19 mmol) and acetic anhydride (0.112 mL, 1.19 mmol). The reaction was stirred at room temperature 1 h. The reaction was quenched with NaHCO3 washed with EtOAc. The organic layer was acidified 1M HCl extracted EtOAc (3×). The combined organics were dried (Na2SO4), filtered and concentrated to give 3-acetoxymethyl-9-carboxy-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepine which was dissolved in ml DCM. A solution of 2.0 M oxalyl chloride in methylene chloride (DCM, 0.357 mL) and 1 drop of DMF was added. The reaction was stirred at room temperature 2 h. The reaction was concentrated to give 3-acetoxymethyl-9-chlorocarbonyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepine which was dissolved in 5 ml acetonitrile. 3-Chloro-N,N-dimethyl-4-(methylamino)benzamide (0.101 g, 0.477 mmol;) and sodium bicarbonate (0.040 g, 0.47 mmol) were added. The reaction was stirred at room temperature overnight. The reaction was quenched water, extracted three times with ethyl acetate, and concentrated. The crude product was purified by flash chromatography (50-100% EtOAc/Hex) (product eluted at 100% EtOAc, sm at 75% EtOAc) to give N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N-methyl-(3-acetoxymethyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepine)-9-carboxamide (41%). MS: (ESI+) 514.3

Workup

  1. concentrationThe reaction mixture was concentrated
  2. extractionthen extracted with EtOAc (3×)
  3. dry with materialThe combined organics were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-cce41cf3fb7d4767b3f5949a3f204d6c
Source dataset
uspto-grants-2014_09
Patent number
US08846762B2

Reaction notes

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