Diisopropylamine → HCID 11831596, compound

HRID 2230918Notes

Reaction equation

HRID 2230918 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1[S:18][C:17]([C:19]([OH:21])=[O:20])=[CH:16][CH:15]=1.Br[CH2:23][CH2:24][CH:25]1[O:29][CH2:28][CH2:27][O:26]1>O1CCCC1.CCCCCC.C(#N)C>[O:26]1[CH2:27][CH2:28][O:29][CH:25]1[CH2:24][CH2:23][CH2:13][C:14]1[S:18][C:17]([C:19]([OH:21])=[O:20])=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 747135-Methylthiophene-2-carboxylic acid2×HCID 877762-(2-Bromoethyl)-1,3-dioxolaneHCID 178418339Butyllithium

Product 1

HCID 11831596HCID 11831596, compoundYield 88.5%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of 64.8 g (640 mmol, 83.9 mL) of diisopropyl amine in 400 mL of tetrahydrofuran which had been cooled to −15° C. was added 400 mL (640 mmol) of 1.6M n-butyllithium in hexane dropwise over 25 minutes, maintaining the reaction temperature below −5° C. After a 15 minute stir time, a solution of 5-methyl-2-thiophenecarboxylic acid (41.4 g, 291 mmol) in 150 mL of tetrahydrofuran was added dropwise over 30 minutes, once again keeping the temperature below −5° C. The resultant dark green dianion solution was stirred at −15° C. to −10° C. for 90 minutes. To this solution was added 2-(2-bromoethyl)-1,3-dioxolane (57.9 g, 320 mmol) dropwise over 15 minutes and the magenta-colored mixture was stirred for 3 hours at −10° C. to −5° C. HPLC analysis (30% acetonitrile/70% 1% aqueous acetic acid solution, 2 mL/min, 30 cm C-18 column, λ=280 nm) at this time showed 9.0% 5-methyl-2-thiophenecarboxylic acid and 88.5% title compound. The reaction was quenched with 600 mL of water and acidified to pH 3 with 6N aqueous hydrochloric acid. The yellow mixture was extracted three times with 500 mL of t-butylmethyl ether and the combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. The crude product was triturated with 300 mL of heptane and the solid was filtered, washed with heptane, and pulled dry on the filter to provide 58.21 g (82.5%) of the title compound which contained less than 3% starting material by 1H NMR. 1H NMR (300 MHz, CDCl3) δ 1.81 (m, 4H), 2.91 (t, J=7.4 Hz, 2H), 3.92 (m, 4H), 4.90 (t, J=4.4 Hz, 1H), 6.84 (d, J=3.7 Hz, 1H), 7.72 (d, J=3.7 Hz, 1H).

Workup

  1. temperaturemaintaining the reaction temperature below −5° C
  2. customthe temperature below −5° C
  3. stirringThe resultant dark green dianion solution was stirred at −15° C. to −10° C. for 90 minutes
  4. stirringthe magenta-colored mixture was stirred for 3 hours at −10° C. to −5° C

Sources & evidence

ORD record
ord-11cd6fcd8011499bb7294a9f38a75fe7
Source dataset
uspto-grants-2002_07
Patent number
US06426417B1

Reaction notes

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