Triethylamine → (S)-ethyl 2-tert-butoxy-2-(6-(cyclopropylethynyl)-1-hydroxy-3-methylnaphthalen-2-yl)acetate

HRID 926189Notes

Reaction equation

HRID 926189 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([O:12][Si](CC)(CC)CC)=[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.[CH:32]1([C:35]#[C:36][Si](C)(C)C)[CH2:34][CH2:33]1.C(N(CC)CC)C.[F-].[Cs+]>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[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:36]#[C:35][CH:32]3[CH2:34][CH2:33]3)[CH:3]=2)[C:8]=1[OH:12])[C:21]([O:23][CH2:24][CH3:25])=[O:22])([CH3:28])([CH3:30])[CH3:29]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 25953Cesium fluorideHCID 2758018(Cyclopropylethynyl)trimethylsilaneHCID 89681729(S)-ethyl 2-(6-bromo-3-methyl-1-(triethylsilyloxy)naphthalen-2-yl)-2-tert-butoxyacetate

Product 1

HCID 89681789(S)-ethyl 2-tert-butoxy-2-(6-(cyclopropylethynyl)-1-hydroxy-3-methylnaphthalen-2-yl)acetate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A Smith process vial was charged (S)-ethyl 2-(6-bromo-3-methyl-1-(triethylsilyloxy)naphthalen-2-yl)-2-tert-butoxyacetate (151 mg, 0.287 mmol), (cyclopropylethynyl)trimethylsilane (195 mg, 0.316 mmol), Pd(PPh3)4 (33 mg, 0.03 mmol), CuI (55 mg, 0.28 mmol), triethylamine (0.12 mL, 0.86 mmol), cesium fluoride (144 mg, 0.95 mmol) and flushed with nitrogen. THF (3 mL) was added and mixture sparged with nitrogen for 10 minutes and then heated in microwave at 110° C. for 1 hour. 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 100% ethyl acetate/hexanes) to give (S)-ethyl 2-tert-butoxy-2-(6-(cyclopropylethynyl)-1-hydroxy-3-methylnaphthalen-2-yl)acetate. LCMS-ESI− (m/z): [M−H]− calcd for C24H27O4: 379.48. Found: 379.20.

Workup

  1. customflushed with nitrogen
  2. additionTHF (3 mL) was added
  3. custommixture sparged with nitrogen for 10 minutes
  4. customReaction mixture
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by flash column chromatography (silica gel, 0 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-18cf909a29854e51bf1a0e6629e0d43f
Source dataset
uspto-grants-2016_03
Patent number
US09284323B2

Reaction notes

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