Potassium Phosphate, Tribasic → HCID 86697128, compound

HRID 237465Notes

Reaction equation

HRID 237465 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:48]([CH3:49])=[CH:47][C:39]([O:40][CH2:41][C:42]([CH3:46])([CH3:45])[CH2:43][OH:44])=[CH:38][C:37]=1[CH3:50].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:36]2[C:48]([CH3:49])=[CH:47][C:39]([O:40][CH2:41][C:42]([CH3:45])([CH3:46])[CH2:43][OH:44])=[CH:38][C:37]=2[CH3:50])=[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

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 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 esterHCID 86697127HCID 86697127, compound

Product 1

HCID 86697128HCID 86697128, compound

Reagents, catalysts & solvents 1

HCID 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 (250 mg), 3-(4-bromo-3,5-dimethylphenoxy)-2,2-dimethylpropan-1-ol (226 mg), K3PO4 (230 mg) are suspended in toluene (2 mL) and water (200 μL) and purged for 10 minutes with argon. Palladium-(II)-acetate (12 mg) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (S-Phos) (44 mg) are added, the vial is sealed and the mixture is stirred at 100° C. for 12 hours. After cooling to room temperature the mixture is partitioned between ethyl acetate and water. The organic phase is washed with brine, dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→60:40) to give the title compound. Yield: 99 mg; LC (method 8): tR=0.87 min; Mass spectrum (ESI+): m/z=549 [M+H]+.

Workup

  1. customwater (200 μL) and purged for 10 minutes with argon
  2. additionPalladium-(II)-acetate (12 mg) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (S-Phos) (44 mg) are added
  3. customthe vial is sealed
  4. temperatureAfter cooling to room temperature the mixture
  5. customis partitioned between ethyl acetate and water
  6. washThe organic phase is washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→60:40)

Sources & evidence

ORD record
ord-f96d5285d39444d2a5ec67a0f6d15552
Source dataset
uspto-grants-2014_02
Patent number
US08642585B2

Reaction notes

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