Phosphorus oxychloride → 10-Chloro-5,6,8,9-tetrahydro-1,4,7,10a-tetraaza-cyclohepta[f]indene-7-carboxylic acid benzyl ester

HRID 528723Notes

Reaction equation

HRID 528723 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:25][CH2:24][C:15]2=[C:16](O)[N:17]3[C:21]([N:22]=[C:14]2[CH2:13][CH2:12]1)=[CH:20][CH:19]=[N:18]3)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:28])=O.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]([N:11]1[CH2:25][CH2:24][C:15]2=[C:16]([Cl:28])[N:17]3[C:21]([N:22]=[C:14]2[CH2:13][CH2:12]1)=[CH:20][CH:19]=[N:18]3)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 178525106HCID 178525106, compound

Product 1

HCID 8666717110-Chloro-5,6,8,9-tetrahydro-1,4,7,10a-tetraaza-cyclohepta[f]indene-7-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a suspension of 3.0 g (8.86 mmol) 10-hydroxy-5,6,8,9-tetrahydro-1,4,7,10a-tetraaza-cyclohepta[f]indene-7-carboxylic acid benzyl ester in 6 mL toluene was added 7 mL (74.06 mmol) of phosphorus oxychloride and 1.28 mL (7.35 mmol) of DIPEA, and the reaction was heated at reflux for 40 minutes. The mixture was cooled to room temperature and poured into ice. The aqueous phase was extracted with DCM (3×20 mL) and the combined organic layers were dried over MgSO4. After filtration and evaporation of the solvent the product was purified by column chromatography (silica, heptane/EtOAc 9:1 to 7:3).

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux for 40 minutes
  3. additionpoured into ice
  4. extractionThe aqueous phase was extracted with DCM (3×20 mL)
  5. dry with materialthe combined organic layers were dried over MgSO4
  6. filtrationAfter filtration and evaporation of the solvent the product
  7. customwas purified by column chromatography (silica, heptane/EtOAc 9:1 to 7:3)

Sources & evidence

ORD record
ord-77e478d9c8024b608e6569b18e70399e
Source dataset
uspto-grants-2016_05
Patent number
US09346816B2

Reaction notes

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