1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → Ethyl 7-(4-(4-bromo-2-chlorophenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate

HRID 510635Notes

Reaction equation

HRID 510635 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]([OH:19])=O)=[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.[Br:38][C:39]1[CH:44]=[CH:43][C:42]([CH2:45][CH2:46][NH2:47])=[C:41]([Cl:48])[CH:40]=1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O>[Br:38][C:39]1[CH:44]=[CH:43][C:42]([CH2:45][CH2:46][NH:47][C:17]([C:16]2[CH:15]=[CH:14][C:13]([O:12][C:11]3[CH:10]=[C:9]4[C:4]([CH:5]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:6][CH2:7][O:8]4)=[CH:3][C:2]=3[Cl:1])=[CH:21][CH:20]=2)=[O:19])=[C:41]([Cl:48])[CH:40]=1

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 670803282-(4-Bromo-2-chlorophenyl)ethanamine

Product 1

HCID 67080296Ethyl 7-(4-(4-bromo-2-chlorophenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylateYield 60.8%

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) (1.15 g. 3.05 mmol), 1-hydroxybenzotriazole hydrate (0.51 g, 3.4 mmol) and 2-(4-bromo-2-chlorophenyl)ethanamine (0.75 g, 3.2 mmol) in N,N-dimethylformamide (10 mL) at ambient temperature was added solid 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.70 g, 3.7 mmol). The resulting solution was stirred at ambient temperature for 17 hours, then diluted with water (100 mL) and extracted with ethyl acetate (100 mL). Addition of 1M hydrochloric acid (20 mL) enabled layer separation. The organic layer was dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel, eluting with 75/25 hexanes/ethyl acetate, to afford ethyl 7-(4-(4-bromo-2-chlorophenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate as an off-white solid (1.10 g, 60% yield).

Workup

  1. extractionextracted with ethyl acetate (100 mL)
  2. additionAddition of 1M hydrochloric acid (20 mL)
  3. customlayer separation
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel
  7. washeluting with 75/25 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-c248dc962a384eee970adf2e9c1386fd
Source dataset
uspto-grants-2015_08
Patent number
US09096567B2

Reaction notes

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