Water → HCID 86684754, compound
Reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([CH2:9][C@@H:10]2[CH2:14][O:13]C(C)(C)[O:11]2)=[CH:4][N:3]=1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.O>C1(C)C=CC=CC=1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([CH2:9][C@@H:10]([OH:11])[CH2:14][OH:13])=[CH:6][C:7]=1[F:8]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 82.5 °C
Procedure
To a solution of 31 (0.70 g, 2.83 mmol) in toluene (8.7 mL) under argon was added 108 (0.69 g, 2.83 mmol), sodium t-butoxide (0.30 g, 3.11 mmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-Phos) (0.20 g, 0.42 mmol). The mixture was degassed with argon and then tris(dibenzylideneacetone) dipalladium (0.26 g, 0.283 mmol) was added. The resulting mixture was stirred at 80-85° C. for 1.5 hrs. Then it was cooled to room temperature, poured onto cold water and extracted with ethyl acetate. The organic layer was separated, washed with brine, and concentrated to an oil which was purified on silica gel with 10% ethyl acetate in hexanes and 20% ethyl acetate in hexanes to afford 0.70 g (59%) of 3 as an amber solid. 1H NMR (CDCl3) δ 1.34 (3 H, s), 1.43 (3 H, s), 1.48 (9 H, s), 1.91 (4 H, m), 2.72 (1 H, m), 2.81 (1 H, m), 3.14 (2 H, d, J=12.04 Hz), 3.61 (1 H, m), 3.71 (2 H, br s), 4.02 (1 H, m), 4.25 (2 H, m), 4.34 (1 H, br s), 7.16 (1 H, d, J=13.98 Hz), 7.83 (1 H, s); LC/MS (M+1) 422.
Workup
- customThe mixture was degassed with argon
- temperatureThen it was cooled to room temperature
- extractionextracted with ethyl acetate
- customThe organic layer was separated
- washwashed with brine
- concentrationconcentrated to an oil which
- customwas purified on silica gel with 10% ethyl acetate in hexanes and 20% ethyl acetate in hexanes
Sources & evidence
- ORD record
- ord-9ee5063ca8344c7e8c58a45483d00ac8
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08921373B2
Reaction notes
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