Water → Butyl 1-{9-[1-(butoxycarbonyl)cyclopentyl]-5-isocyano-5-[(4-methylphenyl)sulfonyl]nonyl}-1-cyclopentanecarboxylate

HRID 750778Notes

Reaction equation

HRID 750778 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([CH2:13][N+:14]#[C-:15])(=[O:12])=[O:11])=[CH:6][CH:5]=1.Br[CH2:17][CH2:18][CH2:19][CH2:20][C:21]1([C:26]([O:28][CH2:29][CH2:30][CH2:31][CH3:32])=[O:27])[CH2:25][CH2:24][CH2:23][CH2:22]1.[OH2:33]>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].CS(C)=O>[CH2:29]([O:28][C:26]([C:21]1([CH2:20][CH2:19][CH2:18][CH2:17][C:13]([N+:14]#[C-:15])([S:10]([C:7]2[CH:6]=[CH:5][C:4]([CH3:3])=[CH:9][CH:8]=2)(=[O:12])=[O:11])[CH2:17][CH2:18][CH2:19][CH2:20][C:21]2([C:26]([O:28][CH2:29][CH2:30][CH2:31][CH3:32])=[O:33])[CH2:25][CH2:24][CH2:23][CH2:22]2)[CH2:25][CH2:24][CH2:23][CH2:22]1)=[O:27])[CH2:30][CH2:31][CH3:32]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydride2×HCID 161915Tosylmethyl isocyanideHCID 21932063Butyl 1-(4-bromo-butyl)-cyclopentanecarboxylate

Product 1

HCID 21932073Butyl 1-{9-[1-(butoxycarbonyl)cyclopentyl]-5-isocyano-5-[(4-methylphenyl)sulfonyl]nonyl}-1-cyclopentanecarboxylate

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

Under a N2 atmosphere, NaH (60% (w/w) in mineral oil, 3.20 g, 80.0 mmol) was added portion wise to a solution of TosMIC (6.58 g, 33.0 mmol) and Bu4NI (1.31 g, 3.55 mmol) in dry DMSO (100 mL) while stirring vigorously and cooling with a water bath. After 30 min, butyl 1-(4-bromo-butyl)-cyclopentanecarboxylate (21.59 g, 67.2 mmol) was added drop wise to the mixture in 20 min and after 1 h of stirring, another portion of NaH (60% (w/w) in mineral oil, 0.56 g, 14 mmol) was added. After 20 min, H2O (250 mL, ice-cold) was added drop wise while cooling with a water bath and the resulting mixture was extracted with Et2O (3×100 mL). The combined organic layers were washed with brine (2×100 mL), dried (Na2SO4) and filtered through a layer of silica. The residue was washed with Et2O (200 mL) and the combined filtrate and washings were evaporated in vacuo. The remaining oil was purified by column chromatography (silica, heptane/EtOAc=8:1) to give butyl 1-{9-[1-(butoxycarbonyl)cyclopentyl]-5-isocyano-5-[(4-methylphenyl)sulfonyl]nonyl}-1-cyclopentanecarboxylate as a yellow oil (13.38 g). This oil (13.38 g) was dissolved in CH2Cl2 (250 mL), and conc aqueous HCl (75 mL) was added. After stirring vigorously for 18 h, H2O (300 mL) was added and the layers were separated. The aqueous phase was extracted with CH2Cl2 (2×100 mL) and the combined organic layers were washed with saturated aqueous NaHCO3 (2×250 mL) and brine (250 mL), dried (Na2SO4) and evaporated in vacuo. The remaining residue was suspended in heptane (100 mL) and filtered. The filtrate was evaporated in vacuo. The remaining residue was purified by column chromatography (silica, heptane/EtOAc=6:1) to give butyl 1-9-[1-(butoxycarbonyl)cyclopentyl]-5-oxononyl-1-cyclopentanecarboxylate (9.05 g, 56%) as a slightly yellow liquid. 1H NMR (CDCl3): δ=4.05 (t, J=6.5 Hz, 4H), 2.36 (t, J=7.5 Hz, 4H), 2.14-2.05 (m, 4H), 1.65-1.32 (m, 28H), 1.24-1.16 (m, 4H), 0.96 (t, J=7.2 Hz, 6H). 13C NMR (CDCl3): δ=210.8, 177.8 (2×), 64.1 (2×), 54.0 (2×), 42.6 (2×), 39.0 (2×), 36.0 (4×), 30.7 (2×), 25.6 (2×), 24.9 (4×), 24.1 (2×), 19.1 (2×), 13.6 (2×). HRMS calcd for C29H50O5(M+): 478.3658, found 478.3663.

Workup

  1. temperaturecooling with a water bath
  2. stirringafter 1 h of stirring
  3. waitAfter 20 min
  4. temperaturewhile cooling with a water bath
  5. extractionthe resulting mixture was extracted with Et2O (3×100 mL)
  6. washThe combined organic layers were washed with brine (2×100 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered through a layer of silica
  9. washThe residue was washed with Et2O (200 mL)
  10. customthe combined filtrate and washings were evaporated in vacuo
  11. customThe remaining oil was purified by column chromatography (silica, heptane/EtOAc=8:1)

Sources & evidence

ORD record
ord-88950aec87ad4a3c9d028ef510838c2d
Source dataset
uspto-grants-2008_07
Patent number
US07405226B2

Reaction notes

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