Triethylamine → Ethyl 6-chloro-7-(4-(4-chloro-2-methoxyphenethylcarbamoyl)phenoxy)chroman-4-carboxylate

HRID 1048194Notes

Reaction equation

HRID 1048194 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][NH2:11])=[C:5]([O:12][CH3:13])[CH:4]=1.C(N(CC)CC)C.[Cl:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[O:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](O)=[O:38])=[CH:35][CH:34]=1)[O:28][CH2:27][CH2:26][CH:25]2[C:42]([O:44][CH2:45][CH3:46])=[O:43].O.N1(O)C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl.CCOC(C)=O>[Cl:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[O:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](=[O:38])[NH:11][CH2:10][CH2:9][C:6]3[CH:7]=[CH:8][C:3]([Cl:2])=[CH:4][C:5]=3[O:12][CH3:13])=[CH:35][CH:34]=1)[O:28][CH2:27][CH2:26][CH:25]2[C:42]([O:44][CH2:45][CH3:46])=[O:43]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acidHCID 670810862-(4-Chloro-2-methoxyphenyl)ethanamine hydrochloride

Product 1

HCID 67080996Ethyl 6-chloro-7-(4-(4-chloro-2-methoxyphenethylcarbamoyl)phenoxy)chroman-4-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 2-(4-chloro-2-methoxyphenyl)ethanamine hydrochloride (Preparation 8; 23.4 g, 105 mmol) in DCM (200 ml) was added triethylamine (16.8 ml, 120 mmol), and the mixture was allowed to stir for 30 minutes (solids did not go into solution). To this was added sequentially 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation 1; 37.8 g, 100 mmol, 1H-benzo[d][1,2,3]triazol-1-ol hydrate (15.4 g, 100 mmol), and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (23.1 g, 120 mmol), and the reaction was allowed to stir overnight (all solids went into solution after 2 hours). The reaction was diluted with EtOAc (600 ml) and washed with 600 mL portions of 1M HCl, saturated aqueous bicarbonate, and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was taken up in hot ethyl acetate (500 ml) and was crystallized by the addition of hexanes (1.5 L) to yield ethyl 6-chloro-7-(4-(4-chloro-2-methoxyphenethylcarbamoyl)phenoxy)chroman-4-carboxylate (51.1 g, 93.9 mmol).

Workup

  1. customPreparation 1
  2. stirringto stir overnight (all solids went into solution after 2 hours)
  3. washwashed with 600 mL portions of 1M HCl, saturated aqueous bicarbonate, and brine
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customwas crystallized by the addition of hexanes (1.5 L)

Sources & evidence

ORD record
ord-f52e3f37b22f4cfb863f4c3b27936e0a
Source dataset
uspto-grants-2013_10
Patent number
US08569522B2

Reaction notes

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