Water → Tert-butyl 1-{9-[1-(tert-butoxycarbonyl)cyclopropyl]-5-isocyano-5-[(4-methylphenyl)sulfonyl]nonyl}-1-cyclopropanecarboxylate

HRID 1469873Notes

Reaction equation

HRID 1469873 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:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:23][CH2:22]1.[OH2:31]>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].CS(C)=O>[C:27]([O:26][C:24]([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:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:31])[CH2:23][CH2:22]2)[CH2:23][CH2:22]1)=[O:25])([CH3:30])([CH3:29])[CH3:28]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 161915Tosylmethyl isocyanideHCID 21932036Tert-Butyl 1-(4-bromobutyl)cyclopropanecarboxylate

Product 1

HCID 21932047Tert-butyl 1-{9-[1-(tert-butoxycarbonyl)cyclopropyl]-5-isocyano-5-[(4-methylphenyl)sulfonyl]nonyl}-1-cyclopropanecarboxylate

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

Under a N2 atmosphere, NaH (60% (w/w) in mineral oil, 2.91 g, 72.8 mmol) was added portion wise to a solution of TosMIC (5.85 g, 30.0 mmol) and Bu4NI (1.10 g, 2.98 mmol) in dry DMSO (100 mL) while stirring vigorously and cooling with a water bath. After 10 min, tert-Butyl 1-(4-bromo-butyl)-cyclopropanecarboxylate (16.56 g, 94% pure by GC, 56.2 mmol) was added drop wise in 20 min and stirring was continued for 1 h and 50 min. Then, H2O (100 mL) was added drop wise 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 evaporated in vacuo. The remaining oil was purified by column chromatography (silica, heptane:EtOAc=6:1) to give tert-butyl 1-{9-[1-(tert-butoxycarbonyl)cyclopropyl]-5-isocyano-5-[(4-methylphenyl)sulfonyl]nonyl}-1-cyclopropanecarboxylate (10.00 g) as a slightly yellow oil. The above mentioned oil (10.00 g) was dissolved in CH2Cl2 (200 mL) and conc aqueous HCl (4 mL) was added. After stirring vigorously for 1 h, H2O (100 mL) was added and the layers were separated. The aqueous phase was extracted with CH2Cl2 (100 mL) and the combined organic layers were washed with saturated aqueous NaHCO3 (3×100 mL), dried (Na2SO4) and evaporated in vacuo. The remaining residue was purified by column chromatography (silica, heptane:EtOAc=10:1) to give tert-butyl 1-[9-[1-(tert-butoxycarbonyl)cyclopropyl]-5-oxononyl]-1-cyclopropanecarboxylate (5.80 g, 49%) as a colorless oil. 1H NMR (CDCl3): δ=2.39 (t, J=7.3 Hz, 4H), 1.63-1.38 (m, 30H), 1.10 (dd, J=6.6, 3.9 Hz, 4H), 0.59 (dd, J=6.7, 3.9 Hz, 4H). 13C NMR (CDCl3): δ=211.1, 174.4 (2×), 79.9 (2×), 42.7 (2×), 33.9 (2×), 28.0 (6×), 27.4 (2×), 24.1 (2×), 24.0 (2×), 15.2 (4×). HRMS calcd for C25H43O5 (MH−): 423.3111, found: 423.3111.

Workup

  1. temperaturecooling with a water bath
  2. stirringstirring
  3. waitwas continued for 1 h and 50 min
  4. extractionthe resulting mixture was extracted with Et2O (3×100 mL)
  5. washThe combined organic layers were washed with brine (2×100 mL)
  6. dry with materialdried (Na2SO4)
  7. customevaporated in vacuo
  8. customThe remaining oil was purified by column chromatography (silica, heptane:EtOAc=6:1)

Sources & evidence

ORD record
ord-0351bdae974f4c29bca6c3e3506f6dac
Source dataset
uspto-grants-2015_04
Patent number
US09006290B2

Reaction notes

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