Lithium Hydroxide → HCID 58883444, compound

HRID 1870041Notes

Reaction equation

HRID 1870041 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:15]2[C:10](=[CH:11][C:12]([C:16]#[C:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C:25]([O:27]C)=[O:26])=[C:20]([F:29])[CH:19]=3)=[CH:13][CH:14]=2)[C:9]([CH3:31])([CH3:30])[CH2:8][CH:7]=1)=[O:5])[CH3:2].[OH-].[Li+]>C(O)C.O1CCCC1>[CH2:1]([O:3][C:4]([C:6]1[C:15]2[C:10](=[CH:11][C:12]([C:16]#[C:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C:25]([OH:27])=[O:26])=[C:20]([F:29])[CH:19]=3)=[CH:13][CH:14]=2)[C:9]([CH3:30])([CH3:31])[CH2:8][CH:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 69071952HCID 69071952, compound2×

Product 1

HCID 58883444HCID 58883444, compoundYield 27.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6-(3-fluoro-4-methoxycarbonylmethyl-phenylethynyl)-4,4-dimethyl-3,4-dihydro-naphthalene-1-carboxylic acid ethyl ester (Intermediate 204, 0.15 g, 0.36 mmol) in ethanol (3 mL) and tetrahydrofuran (3 mL) was treated with a 2M solution of lithium hydroxide (1.5 mL, 3 mmol) and the resulting reaction mixture was stirred at ambient temperature for 1.5 h. The volatiles were evaporated in vacuo, the residue was neutralized with saturated aqueous ammonium chloride solution and extracted with diethyl ether and ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to a residue that was purified by preparative reverse phase HPLC using 5% water in acetonitrile as the mobile phase to afford the title product (0.04 g, 27%). 1H NMR (300 MHz, CDCl3): δ 7.81 (d, J=8.2 Hz, 1H), 7.46 (d, J=1.7 Hz, 1H), 7.37 (dd, J=8.2 &1.7 Hz, 1H), 7.27-7.09 (m, 3H), 7.07 (t, J=4.8 Hz, 1H), 4.31 (q, J=7.0 Hz, 2H), 3.66 (s, 2H), 2.33 (d, J=4.8 Hz, 2H), 1.37 (t, J=7.0 Hz, 3H), 1.27 (s, 6H).

Workup

  1. customthe resulting reaction mixture
  2. customThe volatiles were evaporated in vacuo
  3. extractionextracted with diethyl ether and ethyl acetate
  4. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo to a residue that
  7. customwas purified by preparative reverse phase

Sources & evidence

ORD record
ord-d69fdac798ec4bcdb41250d477976e5d
Source dataset
uspto-grants-2009_12
Patent number
US07638648B2

Reaction notes

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