Chlorodifluoromethane → HCID 86664227, compound

HRID 1184519Notes

Reaction equation

Cl[CH:2]([F:4])[F:3].[OH:5][C:6]1[C:11]2[O:12][CH:13]([CH3:17])[C:14](=[O:16])[NH:15][C:10]=2[CH:9]=[C:8]([CH:18]=[O:19])[CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[F:3][CH:2]([F:4])[O:5][C:6]1[C:11]2[O:12][CH:13]([CH3:17])[C:14](=[O:16])[NH:15][C:10]=2[CH:9]=[C:8]([CH:18]=[O:19])[CH:7]=1

Participants

Conditions

Temperature: 23 °C

Procedure

A 40 mL vial cooled in a dry ice/acetone bath was charged with chlorodifluoromethane (0.209 g, 2.413 mmol) followed by the addition of 8-hydroxy-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde 398A (0.5 g, 2.413 mmol), Cs2CO3 (0.786 g, 2.413 mmol) and DMF (4.83 mL). The dry ice/acetone bath was removed; and with continued stirring, the reaction was slowly warmed to 23° C. After 2.5 hr, the reaction was transferred to a sand bath and stirred at 70° C. for 72 hr. The crude material was purified by prep HPLC-MS (30-55% MeCN in water, basic mode). The fractions were collected and concentrated in vacuo to give the title compound as a white solid (0.404 g, 57% yield): 1H NMR (400 MHz, DMSO-d6) δ ppm 1.44-1.51 (m, 3H) 4.93 (q, J=6.82 Hz, 1H) 7.08-7.28 (m, 1H) 7.32 (d, J=1.77 Hz, 1H) 7.46 (d, J=1.01 Hz, 1H) 9.83-9.88 (m, 1H) 11.14 (s, 1H). ESI-MS: m/z 258.1 (M+H)+.

Workup

temperatureA 40 mL vial cooled in a dry ice/acetone bath
customThe dry ice/acetone bath was removed
customthe reaction was transferred to a sand bath
customThe crude material was purified by prep HPLC-MS (30-55% MeCN in water, basic mode)
customThe fractions were collected
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-3bc579a56a05430ea3f0583ee811a026
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669249B2

Reaction notes

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