p-Methylphenethylamine → Ethyl 6-chloro-7-(4-(4-methylphenethylcarbamoyl)phenoxy)chroman-4-carboxylate

HRID 510629Notes

Reaction equation

HRID 510629 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.C(N=C=NCCCN(C)C)C.[CH3:50][C:51]1[CH:59]=[CH:58][C:54]([CH2:55][CH2:56][NH2:57])=[CH:53][CH:52]=1>CN(C)C=O.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:57][CH2:56][CH2:55][C:54]3[CH:58]=[CH:59][C:51]([CH3:50])=[CH:52][CH:53]=3)=[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 76751p-MethylphenethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid

Product 1

HCID 67080294Ethyl 6-chloro-7-(4-(4-methylphenethylcarbamoyl)phenoxy)chroman-4-carboxylateYield 97.2%

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) (75 mg, 0.20 mmol) and 1-hydroxybenzotriazole hydrate (34 mg, 0.22 mmol) in N,N-dimethylformamide (1 mL) at ambient temperature was added solid 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (47 mg, 0.24 mmol). The resulting solution was stirred at ambient temperature for 20 minutes, and 4-methylphenethylamine (30 mg, 0.23 mmol) was added. After stirring was at ambient temperature for a further 30 minutes, the mixture was diluted with water (10 mL) and extracted with ethyl acetate (5 mL). The organic layer was washed with brine (2 mL), then dried over sodium sulfate and concentrated to afford ethyl 6-chloro-7-(4-(4-methylphenethylcarbamoyl)phenoxy)chroman-4-carboxylate as a colorless oil (96 mg, 96% yield).

Workup

  1. stirringAfter stirring
  2. waitwas at ambient temperature for a further 30 minutes
  3. extractionextracted with ethyl acetate (5 mL)
  4. washThe organic layer was washed with brine (2 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ec79737e60e94df8a9e82d98fcc8adca
Source dataset
uspto-grants-2015_08
Patent number
US09096567B2

Reaction notes

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