Diisopropylamine → HCID 21865357, compound

HRID 856969Notes

Reaction equation

HRID 856969 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][S:14][C:15]1[N:20]=[C:19]([CH3:21])[CH:18]=[CH:17][N:16]=1.[N:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[CH2:28][O:29][C:30]1[CH:31]=[C:32]([CH:39]=[CH:40][CH:41]=1)[C:33](N(OC)C)=[O:34]>O1CCCC1.C(OCC)(=O)C.O>[N:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[CH2:28][O:29][C:30]1[CH:31]=[C:32]([C:33](=[O:34])[CH2:21][C:19]2[CH:18]=[CH:17][N:16]=[C:15]([S:14][CH3:13])[N:20]=2)[CH:39]=[CH:40][CH:41]=1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 8212614-Methyl-2-(methylsulfanyl)pyrimidineHCID 21865375HCID 21865375, compoundHCID 178418339Butyllithium

Product 1

HCID 21865357HCID 21865357, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 22728543Water ethylacetateSolvent

Conditions

Temperature
-75 °C

Procedure

2.1 ml (15 mmol) diisopropylamine were dissolved in 70 ml dry tetrahydrofuran and cooled to −75° C. and 9.4 ml of a solution of n-butyllithium (1.6 M, 15 mmol) were added over a period of 10 minutes. After stirring for 15 minutes at −75° C. a solution of 1.69 g (12 mmol) 2-methylthio-4-methylpyrimidine in 5 ml dry tetrahydrofuran was added within 10 minutes at −75° C. and the mixture was stirred for additional 15 minutes. Then a solution of 2.73 g (7 mmol) B3 (70% purity) in 5 ml dry tetrahydrofuran was added within 10 minutes at −75° C. The mixture was stirred for one hour at −75° C. and then allowed to warm up to room temperature and finally poured on 100 ml ethyl acetate/water (1:1). The aqueous layer was extracted with 50 ml ethyl acetate and the combined organic layers were dried over sodium sulphate. Removal of the solvent in vacuo and column chromatography on Silica (n-heptane/ethyl acetate 3:1) yielded 1.52 g (62%) C1. (keto-enole ratio measured by NMR in CDCl3 at 400 MHz is about 30:70).

Workup

  1. additionwas added within 10 minutes at −75° C.
  2. stirringThe mixture was stirred for one hour at −75° C.
  3. temperatureto warm up to room temperature
  4. extractionThe aqueous layer was extracted with 50 ml ethyl acetate
  5. dry with materialthe combined organic layers were dried over sodium sulphate
  6. customRemoval of the solvent in vacuo and column chromatography on Silica (n-heptane/ethyl acetate 3:1)

Sources & evidence

ORD record
ord-042edbbccfe7457c823cdf4acecd12bf
Source dataset
uspto-grants-2006_12
Patent number
US07144889B2

Reaction notes

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