1,2-Dichloroethane → 1-(3-{2-[3-(2-Hydroxy-ethyl)-phenyl]-ethoxy}-4-methoxy-benzoylamino)-cycloheptanecarboxylic acid methyl ester

HRID 1918315Notes

Reaction equation

HRID 1918315 reaction equation
[OH:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=2[O:22][CH3:23])[C:16]([OH:18])=O)[CH:7]=[CH:8][CH:9]=1.Cl.[CH3:25][O:26][C:27]([C:29]1([NH2:36])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)=[O:28].C(Cl)CCl>CN(C=O)C.C1C=CC2N(O)N=NC=2C=1>[CH3:25][O:26][C:27]([C:29]1([NH:36][C:16](=[O:18])[C:15]2[CH:19]=[CH:20][C:21]([O:22][CH3:23])=[C:13]([O:12][CH2:11][CH2:10][C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([CH2:3][CH2:2][OH:1])[CH:5]=3)[CH:14]=2)[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]1)=[O:28]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 42614177Methyl 1-aminocycloheptane-1-carboxylate hydrochlorideHCID 671707103-{2-[3-(2-Hydroxy-ethyl)-phenyl]-ethoxy}-4-methoxy-benzoic acid

Product 1

HCID 671703341-(3-{2-[3-(2-Hydroxy-ethyl)-phenyl]-ethoxy}-4-methoxy-benzoylamino)-cycloheptanecarboxylic acid methyl esterYield 28.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 757711-HydroxybenzotriazoleSolvent

Procedure

The compound of step 1 (280 mg, 0.885 mmol) was dissolved in DMF (1.3 ml) and HOBT (24 mg), 1-amino-cycloheptanecarboxylic acid methyl ester hydrochloride (221 mg, 1.06 mmol) and EDIA (578 mg, 4.43 mmol) were added. The mixture was cooled in an ice bath and EDC (254 mg, 1.33 mmol) was added. The mixture was stirred at room temperature for 3 days and partitioned between EA and water. The aqueous phase was extracted with EA, the combined organic phases were dried over sodium sulfate and evaporated to dryness. The residue was purified by RP HPLC (water/ACN gradient) to yield the title compound (120 mg).

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. custompartitioned between EA and water
  3. extractionThe aqueous phase was extracted with EA
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. customevaporated to dryness
  6. customThe residue was purified by RP HPLC (water/ACN gradient)

Sources & evidence

ORD record
ord-118e557d1b2141faa30a53b36814380a
Source dataset
uspto-grants-2013_12
Patent number
US08618304B2

Reaction notes

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