Potassium Phosphate, Tribasic → Ethyl 7-(3-(1-amino-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)phenyl)heptanoate

HRID 1874164Notes

Reaction equation

HRID 1874164 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]=[CH2:7].B1C2CCCC1CCC2.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:30]1[CH:31]=[C:32]([C:36]([C:45]2[CH:50]=[C:49]([C:51]([F:54])([F:53])[F:52])[CH:48]=[C:47]([F:55])[CH:46]=2)([NH2:44])[CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:33]=[CH:34][CH:35]=1>C1COCC1.[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>[NH2:44][C:36]([C:32]1[CH:33]=[C:34]([CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]([O:9][CH2:10][CH3:11])=[O:8])[CH:35]=[CH:30][CH:31]=1)([C:45]1[CH:50]=[C:49]([C:51]([F:52])([F:53])[F:54])[CH:48]=[C:47]([F:55])[CH:46]=1)[CH2:37][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 789669-Borabicyclo(3.3.1)nonaneHCID 560341Ethyl 6-heptenoateHCID 594587641-(3-Bromophenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine

Product 1

HCID 59458680Ethyl 7-(3-(1-amino-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)phenyl)heptanoateYield 54%

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl hept-6-enoate (156 mg, 1 mmol) in dry THF (4 mL) cooled in an ice water bath was added a solution of 9-BBN (0.5 M in THF, 2.0 mL, 1 mmol). The cooling bath was removed and the reaction mixture was stirred for 1 h at room temperature. To the reaction mixture was added an aqueous solution of potassium phosphate (3 M, 0.66 mL, 2 mmol) and stirred for an additional 5 min. To the reaction mixture was added a solution of 1-(3-bromophenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine, prepared as described in Procedure 1, (0.2 M in THF, 3 mL, 0.6 mmol), followed by tris-(dibenzylideneacetone) dipalladium(0) (45 mg, 0.04 mmol). The resulting yellow solution was heated under reflux for 20 h. The reaction mixture was cooled and concentrated under reduced pressure. The residue was extracted between water (10 mL) and ether (10 mL). The ether layer was washed twice with water, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (2% to 10% EtOAc in Heptane) to yield ethyl 7-(3-(1-amino-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)phenyl)heptanoate (169 mg, 54% yield). LCMS: RT=3.61 min, Purity 84% [M+H] 516.3 (Sunfire-S5-C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm).

Workup

  1. customThe cooling bath was removed
  2. stirringstirred for an additional 5 min
  3. customprepared
  4. temperatureThe resulting yellow solution was heated
  5. temperatureunder reflux for 20 h
  6. temperatureThe reaction mixture was cooled
  7. concentrationconcentrated under reduced pressure
  8. extractionThe residue was extracted between water (10 mL) and ether (10 mL)
  9. washThe ether layer was washed twice with water
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel flash chromatography (2% to 10% EtOAc in Heptane)

Sources & evidence

ORD record
ord-4d68f792f94743dab665fdfc497b1f1b
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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