Sodium Carbonate → (R)-3-(3,5-Dichloro-4'-methanesulfonyl-biphenyl-4-ylmethyl)-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-one

HRID 1692107Notes

Reaction equation

HRID 1692107 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[C:6]([Cl:32])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][CH:17]([O:20][Si:21]([CH:28]([CH3:30])[CH3:29])([CH:25]([CH3:27])[CH3:26])[CH:22]([CH3:24])[CH3:23])[CH2:16][CH2:15]2)[C:10]1=[O:31].[CH3:41][S:42]([C:45]1[CH:50]=[CH:49][C:48](B(O)O)=[CH:47][CH:46]=1)(=[O:44])=[O:43].C(=O)([O-])[O-].[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>[Cl:1][C:2]1[CH:3]=[C:4]([C:48]2[CH:49]=[CH:50][C:45]([S:42]([CH3:41])(=[O:44])=[O:43])=[CH:46][CH:47]=2)[CH:5]=[C:6]([Cl:32])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][CH:17]([O:20][Si:21]([CH:25]([CH3:26])[CH3:27])([CH:28]([CH3:30])[CH3:29])[CH:22]([CH3:24])[CH3:23])[CH2:16][CH2:15]2)[C:10]1=[O:31]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 86630019trifluoro-methanesulfonic acid 3,5-dichloro-4-[(R)-2-oxo-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-3-ylmethyl]-phenyl ester

Product 1

HCID 66905070(R)-3-(3,5-Dichloro-4'-methanesulfonyl-biphenyl-4-ylmethyl)-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-oneYield 83.4%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
80 °C

Procedure

Bring a mixture of trifluoro-methanesulfonic acid 3,5-dichloro-4-[(R)-2-oxo-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-3-ylmethyl]-phenyl ester (0.14 g, 0.22 mmol), 4-methylsulfonylphenylboronic acid (0.06 g, 0.28 mmol), sodium carbonate (0.07 g, 0.67 mmol) in THF (26 mL) and water (13 mL) to 60° C. To the mixture at 60° C., add Pd(PPh3)4 (0.02 g, 0.01 mmol). Raise the reaction temperature to 80° C. and stir for 1 hour. 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 with 25% to 50% ethyl acetate in hexanes gradient to afford 0.12 g of (R)-3-(3,5-Dichloro-4′-methanesulfonyl-biphenyl-4-ylmethyl)-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-one.

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 with 25% to 50% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-332150ae975144038026473d67b5558a
Source dataset
uspto-grants-2012_04
Patent number
US08153807B2

Reaction notes

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