Sodium Carbonate → HCID 86727495, compound

HRID 519113Notes

Reaction equation

HRID 519113 reaction equation
[CH3:1][C@H: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)=[CH:11][CH:10]=3)=[N:5][NH:4][C:3]1=[O:25].[C:26]([O:30][C:31]([N:33]1[CH2:36][C:35]([CH3:47])([C:37](OS(C(F)(F)F)(=O)=O)=[CH2:38])[CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:26]([O:30][C:31]([N:33]1[CH2:36][C:35]([CH3:47])([C:37]([C:12]2[CH:13]=[C:14]3[C:9](=[CH:10][CH:11]=2)[O:8][CH2:7][C:6]2[N:15]3[C@H:2]([CH3:1])[C:3](=[O:25])[NH:4][N:5]=2)=[CH2:38])[CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 86727453HCID 86727453, compoundHCID 86727496HCID 86727496, compound

Product 1

HCID 86727495HCID 86727495, compoundYield 25.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (R)-4-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Preparation #11, Step E, 2 g, 5.83 mmol), 3-methyl-3-(1-trifluoromethanesulfonyloxy-vinyl)-azetidine-1-carboxylic acid tert-butyl ester (Preparation #20 3.02 g, 8.74 mmol), Na2CO3 (1.235 g, 11.66 mmol) and Pd(Ph3P)4 (3.37 g, 2.91 mmol) in dioxane (20 mL) and water (5 mL) was stirred at 90° C. overnight. 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 0-30% EtOAc in petroleum ether) to give 3-methyl-3-[1-((R)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl)-vinyl]-azetidine-1-carboxylic acid tert-butyl ester (0.610 g, 25%) as a solid. LC/MS (Table 1, Method 25) Rt=0.867 min.; MS m/z: 413 [M+H]+ and 357 [M+H−56]+. 1H NMR (CDCl3, 400 MHz): δ 8.10 (br. s., 1H), 6.98 (d, J=8.4 Hz, 1H), 6.83 (d, J=8.4 Hz, 1H), 6.78 (s, 1H), 5.33 (s, 1H), 5.10 (s, 1H), 4.74 (m, 1H), 4.67-4.56 (d, J=15.2 Hz, 2H), 4.11 (m, 2H), 3.79 (m, 2H), 1.61 (d, J=15.2 Hz, 3H), 1.55 (m, 3H). 1.46 (s, 9H).

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 0-30% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-ab520398b41049dcae953c017dbeb7b1
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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