Sodium Carbonate → HCID 86630017, compound

HRID 1692098Notes

Reaction equation

HRID 1692098 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](OS([C:27]([F:30])([F:29])[F:28])(=O)=O)[CH:5]=[C:6]([Cl:22])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][CH:17]([OH:20])[CH2:16][CH2:15]2)[C:10]1=[O:21].[F:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.[C:41](=O)([O-:43])[O-:42].[Na+].[Na+]>C1COCC1.O.C(OCC)(=O)C.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>[F:30][C:27]([F:28])([F:29])[C:41]([OH:43])=[O:42].[Cl:22][C:6]1[CH:5]=[C:4]([C:35]2[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=2)[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:15][CH2:16][CH:17]([OH:20])[CH2:18][CH2:19]2)[C:10]1=[O:21]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 86630018HCID 86630018, compound

Product 1

HCID 86630017HCID 86630017, compoundYield 17.3%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Bring a mixture of trifluoro-methanesulfonic acid (R)-3,5-dichloro-4-[1-(4-hydroxy-piperidin-1-yl)-2-oxo-pyrrolidin-3-ylmethyl]-phenyl ester (0.102 g, 0.21 mmol), 4-fluorophenylboronic acid (0.035 g, 0.25 mmol), sodium carbonate (0.066 g, 0.62 mmol) in THF (10 mL) and water (3 mL) to 60° C. To the mixture at 60° C., add Pd(PPh3)4 (0.015 g, 0.011 mmol), raise the reaction temperature to 80° C., and stir for 2.5 hours. Cool the reaction, dilute with ethyl acetate, and wash with water and brine. Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and purify on silica gel column and HPLC (Reverse Phase) to afford 0.02 g of the titled product.

Workup

  1. temperatureCool
  2. customthe reaction
  3. washwash with water and brine
  4. dry with materialDry the organic layer (Na2SO4)
  5. customremove the solvent in vacuo
  6. customto afford crude product
  7. custompurify on silica gel column and HPLC (Reverse Phase)

Sources & evidence

ORD record
ord-fe7be5c3b4b14aa48bddef315c53e159
Source dataset
uspto-grants-2012_04
Patent number
US08153807B2

Reaction notes

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