Sodium Carbonate → HCID 86630013, compound

HRID 1692079Notes

Reaction equation

HRID 1692079 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](OS([C:26]([F:29])([F:28])[F:27])(=O)=O)[CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:10]1=[O:20].[F:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.[C:40](=O)([O-:42])[O-:41].[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:29][C:26]([F:27])([F:28])[C:40]([OH:42])=[O:41].[Cl:1][C:2]1[CH:3]=[C:4]([C:34]2[CH:35]=[CH:36][C:31]([F:30])=[CH:32][CH:33]=2)[CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:10]1=[O:20]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 86630015HCID 86630015, compound

Product 1

HCID 86630013HCID 86630013, compoundYield 92%

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-morpholin-4-yl-2-oxo-pyrrolidin-3-ylmethyl)-phenyl ester (0.126 g, 0.26 mmol), 4-fluorophenylboronic acid (0.044 g, 0.31 mmol), sodium carbonate (0.084 g, 0.79 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) and then raise the reaction temperature to 80° C. and stir for 2 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 with 50% ethyl acetate in hexanes to 100% ethyl acetate to afford 0.102 g (92%) of the titled product and then convert to the TFA salt by treating with trifluoroacetic acid. MS (m/z): 423 (M+).

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 50% ethyl acetate in hexanes to 100% ethyl acetate

Sources & evidence

ORD record
ord-4d56bf8ed5904377b088ea0cd5bd7cb8
Source dataset
uspto-grants-2012_04
Patent number
US08153807B2

Reaction notes

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