Triethylamine → (S)-ethyl 2-tert-butoxy-2-(3-methyl-6-(prop-1-ynyl)-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate

HRID 926186Notes

Reaction equation

HRID 926186 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([O:12][S:13]([C:16]([F:19])([F:18])[F:17])(=[O:15])=[O:14])=[C:7]([C@H:20]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:6]([CH3:31])=[CH:5]2.[C:32]([Sn](CCCC)(CCCC)CCCC)#[C:33][CH3:34].C([O-])(O)=O.[Na+].C(N(CC)CC)C>[Pd+2]>[C:27]([O:26][C@@H:20]([C:7]1[C:6]([CH3:31])=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:32]#[C:33][CH3:34])[CH:3]=2)[C:8]=1[O:12][S:13]([C:16]([F:19])([F:17])[F:18])(=[O:15])=[O:14])[C:21]([O:23][CH2:24][CH3:25])=[O:22])([CH3:28])([CH3:29])[CH3:30]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 2733165Tributyl(prop-1-yn-1-yl)stannaneHCID 89681724(S)-ethyl 2-(6-bromo-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)-2-tert-butoxyacetate

Product 1

HCID 118027238(S)-ethyl 2-tert-butoxy-2-(3-methyl-6-(prop-1-ynyl)-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate

Reagents, catalysts & solvents 1

HCID 105144Allyl(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)chloropalladium(II)Catalyst

Conditions

Temperature
120 °C

Procedure

A Smith process vial was charged (S)-ethyl 2-(6-bromo-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)-2-tert-butoxyacetate (55 mg, 0.104 mmol), (1-Propynyl)tributylstannane (35 μL, 0.115 mmol), Chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl)]palladium(II) (8 mg, 0.01 mmol), NaHCO3 (4 mg, 0.05 mmol), triethylamine (44 μL, 0.3 mmol) and flushed with nitrogen. DMF (2.0 mL) was added and mixture sparged with nitrogen for 10 minutes and then heated in microwave at 120° 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-(3-methyl-6-(prop-1-ynyl)-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate. 1H NMR (400 MHz, CDCl3): δ 7.94 (d, J=4.4 Hz, 1H), 7.80 (s, 1H), 7.56 (s, 1H), 7.50 (d, J=4.6 Hz, 1H), 5.63 (s, 1H), 4.08 (m, 2H), 2.52 (s, 3H), 2.08 (s, 3H), 1.21 (s, 9H), 1.18 (t, 3H).

Workup

  1. customflushed with nitrogen
  2. additionDMF (2.0 mL) was added
  3. custommixture sparged with nitrogen for 10 minutes
  4. additionThe reaction mixture was diluted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by flash column chromatography (silica gel, 0 to 20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-92e1eae0849b4b8ab5a481b107102bb4
Source dataset
uspto-grants-2016_03
Patent number
US09284323B2

Reaction notes

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