2-Methyl-3-butyn-2-ol → 2-Tert-butoxy-2-(1-(4-chlorophenyl)-7-(3-hydroxy-3-methylbut-1-ynyl)-3-methylnaphthalen-2-yl)acetic acid

HRID 514072Notes

Reaction equation

HRID 514072 reaction equation
[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][C:16]([C:23]#[C:24][C:25]([OH:28])([CH3:27])[CH3:26])=[CH:17][CH:18]=2)[C:13]=1[C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].BrC1C=C2C(C=C(C)C(C(OC(C)(C)C)C(OCC)=O)=C2C2C=CC(Cl)=CC=2)=CC=1.CC(O)(C#C)C.CCN(CC)CC.[NH4+].[Cl-]>C1COCC1.[Cu]I.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>[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][C:16]([C:23]#[C:24][C:25]([OH:28])([CH3:27])[CH3:26])=[CH:17][CH:18]=2)[C:13]=1[C:29]1[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=1)[C:7]([OH:9])=[O:8])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 5

HCID 82582-Methyl-3-butyn-2-olHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 67126119Ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-7-(3-hydroxy-3-methylbut-1-ynyl)-3-methylnaphthalen-2-yl)acetateHCID 67126201Ethyl 2-(7-bromo-1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)-2-tert-butoxyacetate

Product 1

HCID 565997302-Tert-butoxy-2-(1-(4-chlorophenyl)-7-(3-hydroxy-3-methylbut-1-ynyl)-3-methylnaphthalen-2-yl)acetic acid

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Preparation of ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-7-(3-hydroxy-3-methylbut-1-ynyl)-3-methylnaphthalen-2-yl)acetate: To a solution of ethyl 2-(7-bromo-1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)-2-tert-butoxyacetate (30 mg, 0.061 mmol) in THF (1 mL) was added 2-methylbut-3-yn-2-ol (15 mg, 0.18 mmol), CuI (1 mg, 0.006 mmol), Pd(PPh3)4 (3 mg, 0.003 mmol), and Et3N (50 μL, 0.36 mmol). The reaction mixture was stirred at 65° C. for 1 h. A saturated solution of NH4Cl was added. The layers were separated, and the organic layer was dried, filtered, and concentrated in vacuo. The crude material was purified by column chromatography (EtOAc/hexanes) to give 22 mg of the titled compound. 1H-NMR: 400 MHz, (CD3OD) δ: 7.73 (d, J=9 Hz, 1H), 7.67 (s, 1H), 7.57 (m, 2H), 7.48 (m, 1H), 7.40 (d, J=9 Hz, 1H), 7.29 (d, J=9 Hz, 1H), 7.24 (s, 1H), 5.15 (s, 1H), 4.16 (m, 2H), 2.57 (s, 3H), 1.51 (s, 6H), 1.20 (t, J=7 Hz, 3H), 0.99 (s, 9H).

Workup

  1. customThe layers were separated
  2. customthe organic layer was dried
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by column chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-6b4b1bbbd31d4ddaba0d54ab3a0fbd16
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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