Potassium Carbonate → HCID 86727510, compound

HRID 519124Notes

Reaction equation

HRID 519124 reaction equation
[CH3:1][CH:2]1[N:15]2[C:6]([CH2:7][O:8][C:9]3[C:14]2=[CH:13][C:12](B2OC(C)(C)C(C)(C)O2)=[C:11]([C:25]([F:28])([F:27])[F:26])[CH:10]=3)=[N:5][N:4]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[C:3]1=[O:37].[CH3:38][C:39]1([C:50](OS(C(F)(F)F)(=O)=O)=[CH2:51])[CH2:42][N:41]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:40]1.C(OC(N1CC(C)(C(O)=O)C1)=O)(C)(C)C.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[C:46]([O:45][C:43]([N:41]1[CH2:42][C:39]([CH3:38])([C:50]([C:12]2[CH:13]=[C:14]3[C:9](=[CH:10][C:11]=2[C:25]([F:26])([F:28])[F:27])[O:8][CH2:7][C:6]2[N:15]3[CH:2]([CH3:1])[C:3](=[O:37])[N:4]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:35])([CH3:36])[CH3:34])[N:5]=2)=[CH2:51])[CH2:40]1)=[O:44])([CH3:49])([CH3:48])[CH3:47]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 532341941-(tert-Butoxycarbonyl)-3-methylazetidine-3-carboxylic acidHCID 86727437HCID 86727437, compoundHCID 86727496HCID 86727496, compound

Product 1

HCID 86727510HCID 86727510, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Example #107, Step A, 4.87 g, 6.279 mmol), tert-butyl 3-methyl-3-(1-(trifluoromethylsulfonyloxy)vinyl)azetidine-1-carboxylate (Prepared from 1-(tert-butoxycarbonyl)-3-methylazetidine-3-carboxylic acid using the procedure detailed in Preparation #4, Steps A-C, 2.168 g, 6.279 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.513 g, 0.628 mmol) and K2CO3 (1.735 g, 12.554 mmol) in dioxane (48 mL) and water (8 mL) was stirred at 90° C. for 3 h. The reaction mixture was cooled to ambient temperature. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel (eluting with 0% to 20% EtOAc in petroleum ether) to give 3-methyl-3-{1-[4-methyl-3-oxo-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-vinyl}-azetidine-1-carboxylic acid tert-butyl ester (1.214 g, 31%). LC/MS (Table 1, Method 27) Rt=1.481 min; MS m/z: 633 [M+Na]+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by column chromatography on silica gel (eluting with 0% to 20% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-be7782468faf4ec49b41281bcdd5164b
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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