Triethylamine → (2S)-ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-7-(3-(4-fluorophenyl)-3-hydroxybut-1-ynyl)-3-methylnaphthalen-2-yl)acetate

HRID 926154Notes

Reaction equation

HRID 926154 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([CH3:30])[C:8]([CH:19]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:9]2[C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.[F:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]([OH:42])([C:40]#[CH:41])[CH3:39])=[CH:34][CH:33]=1.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:26]([O:25][C@@H:19]([C:8]1[C:7]([CH3:30])=[CH:6][C:5]2[C:10](=[CH:11][C:2]([C:41]#[C:40][C:38]([C:35]3[CH:34]=[CH:33][C:32]([F:31])=[CH:37][CH:36]=3)([OH:42])[CH3:39])=[CH:3][CH:4]=2)[C:9]=1[C:12]1[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=1)[C:20]([O:22][CH2:23][CH3:24])=[O:21])([CH3:27])([CH3:28])[CH3:29]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 162178622-(4-Fluorophenyl)-3-butyn-2-olHCID 67126201Ethyl 2-(7-bromo-1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)-2-tert-butoxyacetate

Product 1

HCID 89681720(2S)-ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-7-(3-(4-fluorophenyl)-3-hydroxybut-1-ynyl)-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 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of ethyl 2-(7-bromo-1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)-2-tert-butoxyacetate (70 mg, 0.14 mmol) in THF (2 mL) was added 2-(4-fluorophenyl)but-3-yn-2-ol (46 mg, 0.28 mmol), CuI (5 mg, 0.028 mmol), Pd(PPh3)4 (17 mg, 0.014 mmol), and Et3N (80 μL, 0.57 mmol). The reaction mixture was stirred at 70° 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 the titled compound. 1H-NMR: 400 MHz, (CDCl3) δ: 7.56-7.66 (m, 4H), 7.29 (m, 6H), 6.97 (m, 2H), 5.02 (s, 1H), 4.06 (q, J=7 Hz, 2H). 2.54 (s, 3H), 1.76 (s, 3H), 1.10 (s, 9H), 0.80 (t, J=7 Hz, 3H).

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-4b7532d05fa143688700722d4e0a8549
Source dataset
uspto-grants-2016_03
Patent number
US09284323B2

Reaction notes

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