Acetonitrile → (S)-7-bromo-3-(difluoromethoxy)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

HRID 455672Notes

Reaction equation

HRID 455672 reaction equation
[NH2:1][C:2]1[CH2:7][O:6][CH2:5][C@:4]2([C:20]3[CH:19]=[C:18]([OH:21])[N:17]=[CH:16][C:15]=3[O:14][C:13]3[C:8]2=[CH:9][C:10]([Br:22])=[CH:11][CH:12]=3)[N:3]=1.[F-].[Cs+].C(#N)C.[F:28][C:29]([F:41])(S(F)(=O)=O)C(O[Si](C)(C)C)=O>CCOC(C)=O>[Br:22][C:10]1[CH:9]=[C:8]2[C@:4]3([N:3]=[C:2]([NH2:1])[CH2:7][O:6][CH2:5]3)[C:20]3[CH:19]=[C:18]([O:21][CH:29]([F:41])[F:28])[N:17]=[CH:16][C:15]=3[O:14][C:13]2=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 25953Cesium fluorideHCID 2778022Trimethylsilyl 2,2-difluoro-2-(fluorosulfonyl)acetateHCID 178508236HCID 178508236, compound

Product 1

HCID 67438254(S)-7-bromo-3-(difluoromethoxy)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amineYield 19.7%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A flask was charged with (S)-5′-amino-7-bromo-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-3-ol (0.250 g, 0.690 mmol), cesium fluoride (9.17 mg, 0.069 mmol), and acetonitrile (6.90 mL). Trimethylsilyl 2,2-difluoro-2-(fluorosulfonyl)acetate (0.272 mL, 1.381 mmol) was added slowly and the reaction was stirred for 15 minutes. The reaction was diluted with EtOAc and washed with water. The aqueous layer was extracted with EtOAc, and the combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (0-10% MeOH/DCM), to afford (S)-7-bromo-3-(difluoromethoxy)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.056 g, 0.136 mmol, 19.68% yield) as a light yellow solid. [M+H]+=411.9

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe material was purified via column chromatography (0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-5f5fe5ee06204252bd93457ef2ed8611
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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