Water → Ethyl 7-(4-carbamoylphenoxy)-6-chlorochroman-4-carboxylate

HRID 1626410Notes

Reaction equation

N(OCC(C)C)=O.N[C:9]1[CH:31]=[C:30]([C:32](=[O:34])[NH2:33])[CH:29]=[CH:28][C:10]=1[O:11][C:12]1[CH:21]=[C:20]2[C:15]([CH:16]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:17][CH2:18][O:19]2)=[CH:14][C:13]=1[Cl:27].O>CN(C=O)C>[C:32]([C:30]1[CH:31]=[CH:9][C:10]([O:11][C:12]2[CH:21]=[C:20]3[C:15]([CH:16]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:17][CH2:18][O:19]3)=[CH:14][C:13]=2[Cl:27])=[CH:28][CH:29]=1)(=[O:34])[NH2:33]

Participants

Conditions

Temperature: 68.5 °C

Procedure

To a solution of isobutyl nitrite (3.92 g, 15.2 mmol) in DMF (100 mL) at 66° C. was added a solution of ethyl 7-(2-amino-4-carbamoylphenoxy)-6-chlorochroman-4-carboxylate (5.94 g, 15.2 mmol) in DMF (30 mL) dropwise over 14 minutes. The temperature rose to 70° C. during the addition and gas began to evolve. After 37 minutes of stirring at 68-69° C. the resulting solution was cooled to ambient temperature and poured into a reparatory funnel containing water (1500 mL). The resulting mixture was extracted with ethyl acetate (250 mL) and the organic layer was washed with 1M HCl, and brine, dried over sodium sulfate and concentrated to give 5.39 g of brown solid. The solid was triturated with ether and filtered to provide the desired product (4.86 g, 85%).

Workup

additionThe temperature rose to 70° C. during the addition and gas
temperaturewas cooled to ambient temperature
additionpoured into a reparatory funnel
extractionThe resulting mixture was extracted with ethyl acetate (250 mL)
washthe organic layer was washed with 1M HCl, and brine
dry with materialdried over sodium sulfate
concentrationconcentrated

Sources & evidence

ORD record: ord-f9246fb72d4c4513933de75afd673a31
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785445B2

Reaction notes

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