Sodium Carbonate → HCID 90414755, compound

HRID 1526655Notes

Reaction equation

HRID 1526655 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:27])=[C:6]([C@@:8]2([CH:24]([F:26])[F:25])[C@H:14]3[C@H:12]([CH2:13]3)[O:11][C:10]([NH:15][C:16](=[O:23])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:9]2)[CH:7]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2[O:36][C:35]2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:76][O:77][CH2:78][C@@H:79]([NH2:81])[CH3:80]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[C:16]([NH:15][C:10]1[O:11][C@@H:12]2[C@H:14]([C@@:8]([C:6]3[CH:7]=[C:2]([CH:3]=[CH:4][C:5]=3[F:27])[C:35]([NH:81][C@@H:79]([CH3:80])[CH2:78][O:77][CH3:76])=[O:36])([CH:24]([F:26])[F:25])[N:9]=1)[CH2:13]2)(=[O:23])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 70215362-Propanamine, 1-methoxy-, (2S)-HCID 90411896HCID 90411896, compound

Product 1

HCID 90414755HCID 90414755, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A sealable vial was charged with N-((1S,5R,6S)-5-(5-bromo-2-fluorophenyl)-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-yl)benzamide (16e-A, 0.4060 g, 0.924 mmol), palladium acetate (9.34 mg, 0.042 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene ((0.029 g, 0.051 mmol), sodium carbonate (0.058 ml, 1.387 mmol) and toluene (1.849 ml). (S)-(+)-1-Methoxy-2-propylamine (0.195 ml, 1.849 mmol) was added and CO gas was bubbled through the reaction mixture for 10 minutes. The reaction mixture was heated to 80° C. for 3 hours. The reaction mixture was cooled to rt, adsorbed onto a plug of silica gel and purified by flash chromatography, eluting with a gradient of 5% to 80% EtOAc in hexane, to provide 3-((1S,5R,6S)-3-benzamido-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluoro-N—((S)-1-methoxypropan-2-yl)benzamide (0.3780 g, 0.795 mmol, 86% yield).

Workup

  1. customCO gas was bubbled through the reaction mixture for 10 minutes
  2. temperatureThe reaction mixture was cooled to rt
  3. custompurified by flash chromatography
  4. washeluting with a gradient of 5% to 80% EtOAc in hexane

Sources & evidence

ORD record
ord-3734d0a11ece4d51928a2a504124f8bb
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Reaction notes

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