Potassium Phosphate, Tribasic → HCID 118071312, compound

HRID 920852Notes

Reaction equation

HRID 920852 reaction equation
[C:1]([C:4]1[C:5](I)=[N:6][N:7]2[C@H:12]3[CH2:13][O:14][CH2:15][C@H:11]3[N:10]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:9][C:8]=12)(=[O:3])[NH2:2].[Cl:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][C:30]=1[F:31].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[C:1]([C:4]1[C:5]([C:27]2[CH:28]=[CH:29][C:30]([F:31])=[C:25]([Cl:24])[CH:26]=2)=[N:6][N:7]2[C@H:12]3[CH2:13][O:14][CH2:15][C@H:11]3[N:10]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:9][C:8]=12)(=[O:3])[NH2:2]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 118071252HCID 118071252, compound

Product 1

HCID 118071312HCID 118071312, compoundYield 72.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of Intermediate 352F (0.370 g, 0.852 mmol) and (3-chloro-4-fluorophenyl)boronic acid (0.297 g, 1.704 mmol) in dioxane (2 mL) was added a solution of K3PO4 (0.543 g, 2.56 mmol) in water (0.5 mL) and the reaction mixture was purged with nitrogen for 10 min. PdCl2(dppf)CH2Cl2 (0.052 g, 0.064 mmol) was then added and the reaction mixture was heated to 80° C. and stirred for 16 h. The reaction mixture was diluted with water and extracted with EtOAc (3×30 mL). The combined organic layers were washed with water, dried over Na2SO4 and concentrated. The crude compound was purified by silica gel chromatography (12 g REDISEP® column, eluting with 4% MeOH in CHCl3). Fractions containing the product were combined and evaporated to afford Intermediate 352G (0.270 g, 54%) as an off-white solid. MS(ES): m/z=437 [M+H]+.

Workup

  1. customthe reaction mixture was purged with nitrogen for 10 min
  2. extractionextracted with EtOAc (3×30 mL)
  3. washThe combined organic layers were washed with water
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude compound was purified by silica gel chromatography (12 g REDISEP® column, eluting with 4% MeOH in CHCl3)
  7. additionFractions containing the product
  8. customevaporated

Sources & evidence

ORD record
ord-cf58a1c1bc614feda3c775c5ddf23ebc
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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