1-Hydroxybenzotriazole → 7-[2-(5-Chloro-2-isopropoxyphenyl)-2-oxoethylcarbamoyl]heptanoic acid methyl ester

HRID 1616544Notes

Reaction equation

HRID 1616544 reaction equation
C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[CH3:32][O:33][C:34](=[O:44])[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][C:41]([OH:43])=O.Cl.[NH2:46][CH2:47][C:48]([C:50]1[CH:55]=[C:54]([Cl:56])[CH:53]=[CH:52][C:51]=1[O:57][CH:58]([CH3:60])[CH3:59])=[O:49]>C(Cl)Cl>[CH3:32][O:33][C:34](=[O:44])[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][C:41](=[O:43])[NH:46][CH2:47][C:48]([C:50]1[CH:55]=[C:54]([Cl:56])[CH:53]=[CH:52][C:51]=1[O:57][CH:58]([CH3:60])[CH3:59])=[O:49]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5541918-Methoxy-8-oxooctanoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68491544HCID 68491544, compound

Product 1

HCID 591678017-[2-(5-Chloro-2-isopropoxyphenyl)-2-oxoethylcarbamoyl]heptanoic acid methyl esterYield 4,224.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add diisopropylethylamine (99 ml, 568 mmol) dropwise to a solution of EDC HCl (38.01 g, 198 mmol), HOBt (19.19 g, 142 mmol) and octanedioic acid monomethyl ester (53.44 g, 1.42 mmol) in methylene chloride (800 mL) at 0° C. under nitrogen. Warm the mixture to room temperature and stir for 1 hour. Add 2-amino-1-(5-chloro-2-isopropoxyphenyl)ethanone hydrochloride (53.44 g, 142 mmol) to the mixture and stir for 18 hours. Remove the solvent under reduced pressure, dilute the residue in ethyl acetate (300 mL), wash with water (100 mL) and brine (100 mL), and dry over magnesium sulfate. Remove the solvent under reduced pressure and purify the residue by flash column chromatography on silica gel, eluting with hexanes/ethyl acetate (4:6 to 0:10), to afford 7-[2-(5-chloro-2-isopropoxyphenyl)-2-oxoethylcarbamoyl]-heptanoic acid methyl ester (23.87 g, 23% over three steps).

Workup

  1. customRemove the solvent under reduced pressure
  2. additiondilute the residue in ethyl acetate (300 mL)
  3. washwash with water (100 mL) and brine (100 mL)
  4. dry with materialdry over magnesium sulfate
  5. customRemove the solvent under reduced pressure
  6. custompurify the residue by flash column chromatography on silica gel
  7. washeluting with hexanes/ethyl acetate (4:6 to 0:10)

Sources & evidence

ORD record
ord-8fe81f3905014fcc926d5a84fef88875
Source dataset
uspto-grants-2014_07
Patent number
US08765796B2

Reaction notes

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