Potassium Phosphate, Tribasic → HCID 86697203, compound

HRID 237540Notes

Reaction equation

HRID 237540 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.[O:35]=[S:36]1(=[O:54])[CH2:41][CH2:40][C:39]([CH2:43][O:44][C:45]2[CH:50]=[C:49]([CH3:51])[C:48](Br)=[C:47]([CH3:53])[CH:46]=2)([OH:42])[CH2:38][CH2:37]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>CN(C)C=O.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:48]2[C:49]([CH3:51])=[CH:50][C:45]([O:44][CH2:43][C:39]3([OH:42])[CH2:40][CH2:41][S:36](=[O:35])(=[O:54])[CH2:37][CH2:38]3)=[CH:46][C:47]=2[CH3:53])=[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

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 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 esterHCID 86697204HCID 86697204, compound

Product 1

HCID 86697203HCID 86697203, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °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 (190 mg), 1,1-dioxo-4-((4-bromo-3,5-dimethylphenoxy)methyl)tetrahydro-2H-thiopyran-4-ol (150 mg), K3PO4 (250 mg) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (S-Phos) (21 mg) are suspended in N,N-dimethylformamide (2 mL) and water (100 μL). The mixture is purged for 10 minutes with argon. Palladium-(II)-acetate (6 mg) is added, the vial is sealed and the mixture is stirred at 110° C. for 3 hours. After cooling to room temperature the mixture is partitioned between diethylether and saturated aqueous NH4Cl solution. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (petrole ether/ethyl acetate 50:50→0:100) to give the title compound. Yield: 90 mg; LC (method 8): tR=0.53 min; Mass spectrum (ESI+): m/z=625 [M+H]+.

Workup

  1. customThe mixture is purged for 10 minutes with argon
  2. additionPalladium-(II)-acetate (6 mg) is added
  3. customthe vial is sealed
  4. temperatureAfter cooling to room temperature the mixture
  5. customis partitioned between diethylether and saturated aqueous NH4Cl solution
  6. dry with materialThe organic phase is dried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue is chromatographed on silica gel (petrole ether/ethyl acetate 50:50→0:100)

Sources & evidence

ORD record
ord-8fff5f27342e4814b8437caec890736e
Source dataset
uspto-grants-2014_02
Patent number
US08642585B2

Reaction notes

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