Formic Acid → 6-(4-Carboxymethyl-phenylethynyl)-4,4,7-trimethyl-1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid ethyl ester

HRID 1870034Notes

Reaction equation

HRID 1870034 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[C:15]2[C:10](=[CH:11][C:12]([C:17]#[C:18][C:19]3[CH:24]=[CH:23][C:22]([CH2:25][C:26]([O:28]C(C)(C)C)=[O:27])=[CH:21][CH:20]=3)=[C:13]([CH3:16])[CH:14]=2)[C:9]([CH3:34])([CH3:33])[CH2:8][CH2:7]1)=[O:5])[CH3:2].C(O)=O.O>O1CCOCC1>[CH2:1]([O:3][C:4]([CH:6]1[C:15]2[C:10](=[CH:11][C:12]([C:17]#[C:18][C:19]3[CH:24]=[CH:23][C:22]([CH2:25][C:26]([OH:28])=[O:27])=[CH:21][CH:20]=3)=[C:13]([CH3:16])[CH:14]=2)[C:9]([CH3:33])([CH3:34])[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 284Formic AcidHCID 962WaterHCID 690738306-(4-tert-Butoxycarbonylmethyl-phenylethynyl)-4,4,7-trimethyl-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid ethyl ester2×

Product 1

HCID 588834526-(4-Carboxymethyl-phenylethynyl)-4,4,7-trimethyl-1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid ethyl esterYield 74.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 6-(4-tert-butoxycarbonylmethyl-phenylethynyl)-4,4,7-trimethyl-1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid ethyl ester (Intermediate 194, 0.23 g, 0.5 mmol) in 1,4-dioxane (1 mL) was treated with formic acid (3 mL) and the resulting reaction mixture was stirred at ambient temperature for 6 h. Water was added and the reaction mixture was extracted with ethyl acetate (×2). The combined organic phase was washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated to an oil. Preparative reverse phase HPLC using 10% water in acetonitrile as the mobile phase afforded the title compound (0.15 g, 74%). 1H NMR (300 MHz, CDCl3): δ 7.48 (s, 1H), 7.46 (br d, 2H), 7.23 (br d, 2H), 6.96 (s, 1H), 4.17 (q, 2H, J=7.0 Hz), 3.73 (t, 1H, J=5.8 Hz), 3.54 (br s, 2H), 2.40 (s, 3H), 2.29-1.95 (m, 2H), 1.85-1.77 (m, 1H), 1.62-1.44 (m, 1H), 1.31 (s, 3H), 1.26 (s, 3H), 1.25 (t, 3H, buried).

Workup

  1. customthe resulting reaction mixture
  2. extractionthe reaction mixture was extracted with ethyl acetate (×2)
  3. washThe combined organic phase was washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to an oil

Sources & evidence

ORD record
ord-1b5258c4764a403887a5b3b1b0753cbb
Source dataset
uspto-grants-2009_12
Patent number
US07638648B2

Reaction notes

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