Potassium Phosphate, Tribasic → Methyl 2-((S)-6-((R)-4-(4-cyano-2,6-dimethylphenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

HRID 237513Notes

Reaction equation

HRID 237513 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5](B2OC(C)(C)C(C)(C)O2)=[C:6]2[C:10]=1[C@H:9]([O:11][C:12]1[CH:25]=[CH:24][C:15]3[C@H:16]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:17][O:18][C:14]=3[CH:13]=1)[CH2:8][CH2:7]2.Br[C:36]1[C:43]([CH3:44])=[CH:42][C:39]([C:40]#[N:41])=[CH:38][C:37]=1[CH3:45].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:40]([C:39]1[CH:42]=[C:43]([CH3:44])[C:36]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[C:10]3[C:6]=2[CH2:7][CH2:8][C@H:9]3[O:11][C:12]2[CH:25]=[CH:24][C:15]3[C@H:16]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:17][O:18][C:14]=3[CH:13]=2)=[C:37]([CH3:45])[CH:38]=1)#[N:41]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 110850704-Bromo-3,5-dimethyl-benzonitrileHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86697106{(S)-6-[(R)-7-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester

Product 1

HCID 86697175Methyl 2-((S)-6-((R)-4-(4-cyano-2,6-dimethylphenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

In a microwave vial, methyl 2-((S)-6-((R)-7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate (200 mg), 4-bromo-3,5-dimethylbenzonitrile (90 mg), K3PO4 (273 mg), Palladium-(II)-acetate (10 mg) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (S-Phos) (17 mg) are suspended in toluene (10 mL) and water (2 mL) and purged for 10 minutes with argon. The vial is sealed and the mixture is stirred at 100° C. for 4 hours. After cooling to ambient temperature the mixture is partitioned between ethyl acetate and water. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10) to give the title compound. Yield: 85 mg; LC (method 19): tR=1.52 min; Mass spectrum (ESI+): m/z=471 [M+−H]+.

Workup

  1. customwater (2 mL) and purged for 10 minutes with argon
  2. customThe vial is sealed
  3. temperatureAfter cooling to ambient temperature the mixture
  4. customis partitioned between ethyl acetate and water
  5. dry with materialThe organic phase is dried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10)

Sources & evidence

ORD record
ord-924fd9d881824010af812007a8d70a13
Source dataset
uspto-grants-2014_02
Patent number
US08642585B2

Reaction notes

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