Thionyl Chloride → 1-{3-[2-(2-Fluoro-5-methyl-phenyl)-ethoxy]-4-methoxy-benzoylamino}-cycloheptanecarboxylic acid methyl ester

HRID 1475690Notes

Reaction equation

HRID 1475690 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH2:9][CH2:10][O:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[C:15]([OH:17])=O.S(Cl)(Cl)=O.Cl.[CH3:28][O:29][C:30]([C:32]1([NH2:39])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)=[O:31].C(=O)([O-])O.[Na+]>CC(=O)OCC>[CH3:28][O:29][C:30]([C:32]1([NH:39][C:15](=[O:17])[C:14]2[CH:18]=[CH:19][C:20]([O:21][CH3:22])=[C:12]([O:11][CH2:10][CH2:9][C:3]3[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=3[F:1])[CH:13]=2)[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]1)=[O:31]

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 42614177Methyl 1-aminocycloheptane-1-carboxylate hydrochlorideHCID 671705643-[2-(2-Fluoro-5-methyl-phenyl)-ethoxy]-4-methoxy-benzoic acid

Product 1

HCID 671692161-{3-[2-(2-Fluoro-5-methyl-phenyl)-ethoxy]-4-methoxy-benzoylamino}-cycloheptanecarboxylic acid methyl esterYield 37.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

The compound of step 2 (285 mg, 0.937 mmol) was dissolved in an excess of thionyl chloride (0.7 ml) and stirred for 20 min at 60° C. The solution was evaporated to dryness in vacuo. The residue was dissolved in a little DCM and added to a well-stirred mixture of 1-amino-cycloheptanecarboxylic acid methyl ester hydrochloride (195 mg, 0.937 mmol), EA and an excess of a saturated aqueous sodium hydrogencarbonate solution. The mixture was stirred for 30 min at room temperature. The layers were separated, the aqueous phase was extracted with EA, the combined organic phases were washed with brine, dried over sodium sulfate, filtered and evaporated to dryness. This residue was purified by preparative RP HPLC (water/ACN gradient) to give 160 mg of the title compound.

Workup

  1. customThe solution was evaporated to dryness in vacuo
  2. dissolutionThe residue was dissolved in a little DCM
  3. stirringThe mixture was stirred for 30 min at room temperature
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with EA
  6. washthe combined organic phases were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customThis residue was purified by preparative RP HPLC (water/ACN gradient)

Sources & evidence

ORD record
ord-0e7e777566214c4f9ff457a4d3294e2b
Source dataset
uspto-grants-2015_04
Patent number
US09018383B2

Reaction notes

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