Water → HCID 86684754, compound

HRID 1408894Notes

Reaction equation

HRID 1408894 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

7

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

  1. customThe mixture was degassed with argon
  2. temperatureThen it was cooled to room temperature
  3. extractionextracted with ethyl acetate
  4. customThe organic layer was separated
  5. washwashed with brine
  6. concentrationconcentrated to an oil which
  7. 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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