N,N-Dimethylglycine → Ethyl 6-chloro-7-(4-(4-chlorophenethylcarbamoyl)-2-methylphenoxy)chroman-4-carboxylate

HRID 1021538Notes

Reaction equation

Br[C:2]1[CH:19]=[CH:18][C:5]([C:6]([NH:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[O:7])=[CH:4][C:3]=1[CH3:20].[Cl:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[OH:32])[O:28][CH2:27][CH2:26][CH:25]2[C:33]([O:35][CH2:36][CH3:37])=[O:34].CN(C)CC(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[Cu]Cl>[Cl:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[O:32][C:2]1[CH:19]=[CH:18][C:5]([C:6](=[O:7])[NH:8][CH2:9][CH2:10][C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)=[CH:4][C:3]=1[CH3:20])[O:28][CH2:27][CH2:26][CH:25]2[C:33]([O:35][CH2:36][CH3:37])=[O:34]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4-bromo-N-(4-chlorophenethyl)-3-methylbenzamide (0.0831 g, 0.236 mmol), ethyl 6-chloro-7-hydroxychroman-4-carboxylate (0.050 g, 0.195 mmol), and 2-(dimethylamino)acetic acid (0.0104 g, 0.101 mmol) in dioxane (1 ml) degassed with argon was added cesium carbonate (0.133 g, 0.409 mmol) and copper(I) chloride (0.0100 g, 0.101 mmol). The reaction was sealed in a screw-cap vial and heated to 100° C. for 16 hours. The reaction was cooled to ambient temperature, then loaded directly onto a Biotage SP1 system, eluting with a linear gradient of 5-70% EtOAc in hexanes to yield 22 mg of the title compound (21% yield).

Workup

customThe reaction was sealed in a screw-cap vial and
temperatureThe reaction was cooled to ambient temperature
washeluting with a linear gradient of 5-70% EtOAc in hexanes

Sources & evidence

ORD record: ord-9f93ce1470ba4e7fa9bcd091181733e5
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08716498B2

Reaction notes

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