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

HRID 873258Notes

Reaction equation

HRID 873258 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 portionwise 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, 103b (16.56 g, 94% pure by GC, 56.2 mmol) was added dropwise in 20 min and stirring was continued for 1 h and 50 min. Then, H2O (100 mL) was added dropwise and the resulting mixture was extracted with Et2O (3×100 mL). The combined organic layers were washed with brine (2×100 mL) and dried. The remaining oil was purified by column chromatography (silica, heptane:EtOAc=6:1) to give t-butyl 1-{9-[1-(t-butoxycarbonyl)cyclopropyl]-5-isocyano-5-[(4-methylphenyl)sulfonyl]nonyl}-1-cyclopropanecarboxylate (10.00 g) as a slightly yellow oil.

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. customdried
  7. customThe remaining oil was purified by column chromatography (silica, heptane:EtOAc=6:1)

Sources & evidence

ORD record
ord-3c5d986a06c64a7cb596329f480c1c77
Source dataset
uspto-grants-2015_03
Patent number
US08975300B2

Reaction notes

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