Phenylboronic Acid → HCID 69171162, compound

HRID 2374449Notes

Reaction equation

HRID 2374449 reaction equation
[C:1]([O:5][C:6](=[O:32])[CH2:7][CH2:8][N:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24](Cl)=[C:23]([C:28]([F:31])([F:30])[F:29])[CH:22]=3)[CH:15]=2)[CH2:10]1)([CH3:4])([CH3:3])[CH3:2].[C:33]1(B(O)O)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C1(P(C2C=CC=CC=2C2C=CC=CC=2)C2CCCCC2)CCCCC1.[F-].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].C1COCC1>[C:1]([O:5][C:6](=[O:32])[CH2:7][CH2:8][N:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[C:23]([C:28]([F:31])([F:30])[F:29])[CH:22]=3)[CH:15]=2)[CH2:10]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 66827Phenylboronic AcidHCID 522689Potassium FluorideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 691740893-[6-(4-chloro-3-trifluoromethyl-phenoxymethyl)-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid tert-butyl ester

Product 1

HCID 69171162HCID 69171162, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial is charged with 3-[6-(4-chloro-3-trifluoromethyl-phenoxymethyl)-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid tert-butyl ester (56 mg, 0.119 mmol), phenylboronic acid (17 mg, 1.2 eq.), Pd(OAc)2 (1.3 mg, 5 mol %), (dicyclohexylphosphino)biphenyl (4.2 mg, 10 mol %), KF (21 mg, 3 eq.), and THF (0.25 mL). The resulting mixture is heated to 120° C. using microwave irradiation for 20 minutes. The mixture is filtered through celite. The celite is washed with EtOAc several times. The filtrate is then concentrated to give a dark oil. The mixture is purified by column chromatography (silica gel, EtOAc/Hexane, gradient) to give 3-[6-(2-trifluoromethyl-biphenyl-4-yloxymethyl)-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid tert-butyl ester.

Workup

  1. custommicrowave irradiation for 20 minutes
  2. filtrationThe mixture is filtered through celite
  3. washThe celite is washed with EtOAc several times
  4. concentrationThe filtrate is then concentrated
  5. customto give a dark oil
  6. customThe mixture is purified by column chromatography (silica gel, EtOAc/Hexane, gradient)

Sources & evidence

ORD record
ord-c6932c5e352b4a79b4e1aefcbc705ecf
Source dataset
uspto-grants-2008_12
Patent number
US07462629B2

Reaction notes

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