Water → HCID 14892337, compound

HRID 1919697Notes

Reaction equation

HRID 1919697 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]1[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:26]([Li])CCC.IC.O>C1COCC1.CCOCC>[C:1]([O:5][C:6]([N:8]1[C:13]([CH3:26])=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]1[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 14892331HCID 14892331, compoundHCID 178418339Butyllithium

Product 1

HCID 14892337HCID 14892337, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-42 °C

Procedure

To a stirred solution of 1-(tert-Butoxycarbonyl)-4-chloro-2-n-undecyl-1,2-dihydropyridine (3.15, 8.51 mmol) in 115 ml of THF at −42° C. was added n-butyllithium (6.4 mL, 10.2 mmol, 1.6 M solution in hexanes) dropwise via syringe. After the mixture had stirred at −42° C. for 1 h, iodomethane (1.6 mL, 25.54 mmol) was added and stirring was continued at −42° C. for 1 h and then at room temperature for 1 h. Water (30 mL) and ether (60 mL) were added, the layers were separated, the aqueous phase was extracted with ether (2×15 mL), and the combined organic extracts were washed with brine. The organic phase was dried over K2CO3 filtered through silica gel/Celite, and concentrated in vacuo to give the crude product. Purification by column chromatography gave with 5% EtOAc in hexanes afforded 2.5 g (77%) of the product as a clear orange oil which was homogeneous by TLC analysis. 1H NMR (250 MHz) d 5.62 (dd, 1H), 5.30 (m, 1H), 4.76 (dt 1H), 2.16 (s, 3H), 1.53 (s, 9H), 1.48-1.40 (m, 2H), 1.26 (br s, 18H), 0.84 (t, 3H); 13C NMR (62.7 MHz) 153.1 (s), 137.1 (s), 126.6 (s), 119.4 (s), 112.3 (s), 81.4 (s), 54.2 (s), 31.9 (s), 31.8 (s), 29.69 (s), 29.63 (s), 29.55 (s), 29.44 (s), 29.36 (s), 29.33 (s), 28.2 (s), 24.6 (s), 22.7 (s), 22.0 (s), 14.1 (s) ppm. FT-IR (neat) 2956, 2924, 2852, 1709, 1637, 1471, 1393, 1368, 1342, 1169, 1131 cm−1.

Workup

  1. stirringstirring
  2. waitwas continued at −42° C. for 1 h
  3. waitat room temperature for 1 h
  4. customthe layers were separated
  5. extractionthe aqueous phase was extracted with ether (2×15 mL)
  6. washthe combined organic extracts were washed with brine
  7. dry with materialThe organic phase was dried over K2CO3
  8. filtrationfiltered through silica gel/Celite
  9. concentrationconcentrated in vacuo
  10. customto give the crude product
  11. customPurification by column chromatography
  12. customgave with 5% EtOAc in hexanes

Sources & evidence

ORD record
ord-e35ffbdcab574882991d944b347862c4
Source dataset
uspto-grants-2012_05
Patent number
US08168657B2

Reaction notes

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