Potassium Carbonate → 5-(2-Bromo-5-fluoro-pyridin-4-yl)-2,2-bis-fluoromethyl-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

HRID 538372Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[C:6]([C:8]([NH:19]S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)([CH3:18])[CH2:9][O:10][C:11]([C:16]#[N:17])([CH2:14][F:15])[CH2:12][F:13])[C:5]([F:32])=[CH:4][N:3]=1.C(N[C@H](C(O)=O)CS)(=O)C.C([O-])([O-])=O.[K+].[K+]>CCO>[Br:1][C:2]1[CH:7]=[C:6]([C:8]2([CH3:18])[CH2:9][O:10][C:11]([CH2:14][F:15])([CH2:12][F:13])[C:16]([NH2:17])=[N:19]2)[C:5]([F:32])=[CH:4][N:3]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A solution of N-[1-(2-bromo-5-fluoro-pyridin-4-yl)-2-(cyano-bis-fluoromethyl-methoxy)-1-methyl-ethyl]-2-nitro-benzenesulfonamide (840 mg, 1.563 mmol), N-acetyl-L-cysteine (510 mg, 3.13 mmol) and K2CO3 (432 mg, 3.130 mmol) in abs. EtOH (10 ml) was stirred at 85° C. for 18 h. N-acetyl-L-cysteine (250 mg, 1.533 mmol) and K2CO3 (210 mg, 1.519 mmol) was added and stirring at 85° C. was continued for 18 h. The reaction mixture was concentrated to ⅓ of its volume, quenched with 10% aq. K2CO3 soln. and 3× extracted with TBME. The combined org. phases were washed with sat. aq. NaHCO3 soln, brine, dried over Na2SO4, filtered and concentrated to leave the crude title compound that was purified by NP-HPLC (Alltech Grom Saphir65 Si 10 μm column, 150×30 mm, gradient n-heptane:EtOAc:MeOH 68:30:2 to 0:65:35),

Workup

concentrationThe reaction mixture was concentrated
customquenched with 10% aq. K2CO3 soln
extractionand 3× extracted with TBME
washphases were washed with sat. aq. NaHCO3 soln
dry with materialbrine, dried over Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-223523e477914de296bfbee6393db119
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08865712B2

Reaction notes

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