Potassium Phosphate, Tribasic → HCID 86619683, compound

HRID 1675279Notes

Reaction equation

HRID 1675279 reaction equation
Cl[C:2]1[CH:27]=[CH:26][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([C@@H:14]([C:21]3[CH:25]=[CH:24][O:23][N:22]=3)[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[O:28][C:29]([F:32])([F:31])[F:30].[CH3:33][C:34]1([CH3:48])[C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][CH2:36][CH2:35]1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:33][C:34]1([CH3:48])[C:35]([C:2]2[CH:27]=[CH:26][C:5]([CH2:6][O:7][C:8]3[CH:13]=[CH:12][C:11]([C@@H:14]([C:21]4[CH:25]=[CH:24][O:23][N:22]=4)[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:10][CH:9]=3)=[CH:4][C:3]=2[O:28][C:29]([F:32])([F:31])[F:30])=[CH:36][CH2:37][CH2:38]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 574675872-(5,5-Dimethylcyclopent-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 59300674HCID 59300674, compound

Product 1

HCID 86619683HCID 86619683, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

Compound 35.4 (1.60 g, 3.40 mmol), 36.3 (0.91 g, 4.10 mmol), Pd(OAc)2 (0.11 g, 0.51 mmol), S-phos (0.42 g, 1.02 mmol) and K3PO4 were added to a flask. The flask was flushed with nitrogen and charged with dioxane (9.0 mL) and water (3.0 mL). The mixture was then stirred at 80° C. overnight. The solvent was removed, and the residue was purified by column chromatography to give an intermediate, (S)-ethyl 3-(4-(4-(5,5-dimethylcyclopent-1-enyl)-3-(trifluoromethoxy)benzyloxy)-phenyl)-3-(isoxazol-3-yl)propanoate (0.45 g, 0.85 mmol) that was treated with LiOH (1.0 mL, 3.33 M in water) in MeOH (6.0 mL) at room temperature overnight. The reaction mixture was purified by preparative HPLC (reverse phase) to give the title compound 36. 1H NMR (CD3CN) δ 1.04 (s, 6 H), 1.85 (m, 2 H), 2.41 (m, 2 H), 2.97 (dd, J=7.5, 16.4 Hz, 1 H), 3.17 (dd, J=7.5, 16.4 Hz, 1H), 4.52 (m, 1 H), 5.07 (s, 2 H), 5.26 (m, 1 H), 6.23 (d, J=1.5 Hz, 1 H), 6.94 (d, J=6.6 Hz, 2 H), 7.22 (d, J=6.6 Hz, 2 H), 7.35-7.39 (m, 3 H), 8.41, (d, J=1.5 Hz, 1 H). MS ESI (pos.) m/e: 502 (M+H).

Workup

  1. customThe flask was flushed with nitrogen
  2. additioncharged with dioxane (9.0 mL) and water (3.0 mL)
  3. customThe solvent was removed
  4. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-4f94732d742140c293af2f41ec549636
Source dataset
uspto-grants-2011_08
Patent number
US08003648B2

Reaction notes

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