1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → Ethyl 6-chloro-7-(4-(2,4-dichloro-6-methoxyphenethylcarbamoyl)phenoxy)chroman-4-carboxylate

HRID 510800Notes

Reaction equation

HRID 510800 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23].O.ON1C2C=CC=CC=2N=N1.[Cl:38][C:39]1[CH:44]=[C:43]([Cl:45])[CH:42]=[C:41]([O:46][CH3:47])[C:40]=1[CH2:48][CH2:49][NH2:50].Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](=[O:18])[NH:50][CH2:49][CH2:48][C:40]3[C:41]([O:46][CH3:47])=[CH:42][C:43]([Cl:45])=[CH:44][C:39]=3[Cl:38])=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23]

Participants

7

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acidHCID 670803092-(2,4-Dichloro-6-methoxyphenyl)ethanamine

Product 1

HCID 67080749Ethyl 6-chloro-7-(4-(2,4-dichloro-6-methoxyphenethylcarbamoyl)phenoxy)chroman-4-carboxylateYield 48.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation 1; 0.75 g; 2.0 mmol), 1-hydroxybenzotriazole hydrate, and 2-(2,4-dichloro-6-methoxyphenyl)ethanamine (Preparation 7; 0.48 g, 2.19 mmol) in 6 mL DMF at ambient temperature was added solid 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.46 g; 2.4 mmol). The resulting solution was stirred at ambient temperature overnight for convenience. The solution was diluted with 60 mL water and after stirring for 10 minutes, the mixture was transferred to a separatory funnel and extracted with 30 mL EtOAc. 1M HCl (30 mL) was added to enable layer separation. The organic layer was dried over sodium sulfate and evaporated. The residue was purified by silica gel chromatography on a Biotage 40M column, eluting with 70/30 hexane/EtOAc, to give 0.56 g of ethyl 6-chloro-7-(4-(2,4-dichloro-6-methoxyphenethylcarbamoyl)phenoxy)chroman-4-carboxylate as a white glass. MS (apci, pos) m/z=578.

Workup

  1. stirringafter stirring for 10 minutes
  2. customthe mixture was transferred to a separatory funnel
  3. extractionextracted with 30 mL EtOAc
  4. addition1M HCl (30 mL) was added
  5. customlayer separation
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. customevaporated
  8. customThe residue was purified by silica gel chromatography on a Biotage 40M column
  9. washeluting with 70/30 hexane/EtOAc

Sources & evidence

ORD record
ord-7eb83a4043ba4ab7b8ac4b2cf8ff4473
Source dataset
uspto-grants-2015_08
Patent number
US09096567B2

Reaction notes

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