Potassium Carbonate → 5'-[(R)-2-Carboxy-1-(2-chloro-benzyl)-ethylcarbamoyl]-2'-methyl-biphenyl-2-carboxylic Acid

HRID 2361133Notes

Reaction equation

HRID 2361133 reaction equation
C([O:3][C:4](=[O:26])[CH2:5][C@H:6]([NH:15][C:16](=[O:25])[C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[C:19](Br)[CH:18]=1)[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:14])C.C([O:31][C:32]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1B1OC(C)(C)C(C)(C)O1)=[O:33])(C)(C)C.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>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.CCOC(C)=O.C1COCC1.CCO.C1(C)C=CC=CC=1>[C:4]([CH2:5][C@H:6]([NH:15][C:16]([C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[C:19]([C:35]2[C:34]([C:32]([OH:33])=[O:31])=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:18]=1)=[O:25])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:14])([OH:3])=[O:26]

Participants

11

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 4376764Tert-butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 71073749(R)-3-(3-bromo-4-methyl-benzoylamino)-4-(2-chloro-phenyl)-butyric acid ethyl ester

Product 1

HCID 710737985'-[(R)-2-Carboxy-1-(2-chloro-benzyl)-ethylcarbamoyl]-2'-methyl-biphenyl-2-carboxylic Acid

Reagents, catalysts & solvents 6

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

(R)-3-(3-Bromo-4-methyl-benzoylamino)-4-(2-chloro-phenyl)-butyric acid ethyl ester (103 mg, 235 μmol, 1.0 eq.) was combined with 2-t-butoxycarbonylphenylboronic acid pinacol ester (85.9 mg, 282 μmol, 1.2 eq.). Toluene (328 μL) was added followed by EtOH (180 μL) then K2CO3 (65.1 mg, 471 μmol, 2.0 eq.) predissolved in water (61.5 μL). The mixture was stirred to aid in dissolution. The reaction vessel was purged with nitrogen then Pd(PPh3)4 (27.2 mg, 23.5 μmol) was added quickly. The reaction vessel was capped and heated to 100° C. for 30 minutes. The organics were removed and evaporated under vacuum. 1:1 TFA/DCM (0.2 mL each) was added and the resulting mixture was stirred for 30 minutes. The solvents were evaporated and THF (3 mL) and 1 M aqueous NaOH (706 μL, 3.0 eq.) were added. The mixture was stirred for 2 hours and EtOAc was added.

Workup

  1. dissolutionto aid in dissolution
  2. customThe reaction vessel was purged with nitrogen
  3. customThe reaction vessel was capped
  4. customThe organics were removed
  5. customevaporated under vacuum
  6. addition1:1 TFA/DCM (0.2 mL each) was added
  7. stirringthe resulting mixture was stirred for 30 minutes
  8. customThe solvents were evaporated
  9. stirringThe mixture was stirred for 2 hours

Sources & evidence

ORD record
ord-20daa0f2dbdb4f4793451399efb8fe56
Source dataset
uspto-grants-2014_04
Patent number
US08686184B2

Reaction notes

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