Tetrahydrofuran → (S)-ethyl 2-tert-butoxy-2-(1-cyclohexenyl-3-methylnaphthalen-2-yl)acetate

HRID 514009Notes

Reaction equation

HRID 514009 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1Cl)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[C:24]1(B(O)O)[CH2:29][CH2:28][CH2:27][CH2:26][CH:25]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1COCC1>CC(OC)(C)C.COC1C=CC=C(OC)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].O>[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[C:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH:25]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 38629021-Cyclohexenylboronic acidHCID 68085812(S)-ethyl 2-tert-butoxy-2-(1-chloro-3-methylnaphthalen-2-yl)acetate

Product 1

HCID 86691533(S)-ethyl 2-tert-butoxy-2-(1-cyclohexenyl-3-methylnaphthalen-2-yl)acetateYield 46.7%

Reagents, catalysts & solvents 2

HCID 71311105SPhos PalladacycleCatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A Smith process vial was charged with (S)-ethyl 2-tert-butoxy-2-(1-chloro-3-methylnaphthalen-2-yl)acetate (15 mg, 0.045 mmol, 1 eq.), cyclohexenylboronic acid (9 mg, 1.5 eq.), Sphos precatalyst (5 mg, 15%) and potassium phosphate (29 mg, 3 eq.), THF (0.2 mL) and water (0.2 mL) was added and mixture sparged with nitrogen for 10 minutes and then heated in microwave at 110° C. for 1 hour. The reaction mixture was diluted with ethyl acetate and washed with brine, dried (MgSO4), filtered, concentrated and purified by flash column chromatography (silica gel, 0 to 20% ethyl acetate/hexanes) to give (S)-ethyl 2-tert-butoxy-2-(1-cyclohexenyl-3-methylnaphthalen-2-yl)acetate (8 mg). Analytical HPLC (Gemini, 2-98% ACN/H2O+0.05% TFA, 10 minutes run): tR (min)=7.06.

Workup

  1. additionwas added
  2. custommixture sparged with nitrogen for 10 minutes
  3. additionThe reaction mixture was diluted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by flash column chromatography (silica gel, 0 to 20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-54743798eb5b4aabad49bec43b4f794c
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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