Tetrahydrofuran → (S)-ethyl 2-(1-(3-(azetidin-1-yl)phenyl)-3-methylnaphthalen-2-yl)-2-tert-butoxyacetate

HRID 514019Notes

Reaction equation

HRID 514019 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].CC1(C)C(C)(C)OB([C:32]2[CH:33]=[C:34]([N:38]3[CH2:41][CH2:40][CH2:39]3)[CH:35]=[CH:36][CH:37]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1COCC1>O>[N:38]1([C:34]2[CH:33]=[C:32]([C:13]3[C:14]4[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=4)[CH:20]=[C:21]([CH3:22])[C:12]=3[C@H:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:37]=[CH:36][CH:35]=2)[CH2:41][CH2:40][CH2:39]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 583451801-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)azetidineHCID 68085812(S)-ethyl 2-tert-butoxy-2-(1-chloro-3-methylnaphthalen-2-yl)acetate

Product 1

HCID 68085982(S)-ethyl 2-(1-(3-(azetidin-1-yl)phenyl)-3-methylnaphthalen-2-yl)-2-tert-butoxyacetate

Reagents, catalysts & solvents 1

HCID 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 (60.5 mg, 0.181 mmol), 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)azetidine (93.7 mg, 0.361 mmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]Pd(II)methyl-t-butyl ether adduct (12.2 mg, 0.0181 mmol) and potassium phosphate (153 mg, 0.543 mmol), THF (2 mL) and water (1 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, ethyl acetate/hexanes) to the desired product containing some impurities that was used in the next step without further purification.

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, ethyl acetate/hexanes) to the desired product
  9. additioncontaining some impurities that
  10. customwas used in the next step without further purification

Sources & evidence

ORD record
ord-261c552dbaeb4412a10f2a664825079f
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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