2-Chlorobenzenesulfonyl chloride → 8-(2-Chloro-benzenesulfonyl)-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decane-1,7-dione

HRID 420652Notes

Reaction equation

HRID 420652 reaction equation
[F:1][C:2]([F:23])([F:22])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:14][CH2:13][C:12]3([CH2:19][CH2:18][NH:17][C:16](=[O:20])[CH2:15]3)[C:11]2=[O:21])=[CH:6][CH:5]=1.C([Li])CCC.[Cl:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[S:36](Cl)(=[O:38])=[O:37]>C1COCC1>[Cl:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[S:36]([N:17]1[CH2:18][CH2:19][C:12]2([C:11](=[O:21])[N:10]([C:7]3[CH:8]=[CH:9][C:4]([O:3][C:2]([F:1])([F:22])[F:23])=[CH:5][CH:6]=3)[CH2:14][CH2:13]2)[CH2:15][C:16]1=[O:20])(=[O:38])=[O:37]

Participants

5

Reactant 3

HCID 761872-Chlorobenzenesulfonyl chlorideHCID 584784112-(4-Trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decane-1,7-dione2×HCID 178418339Butyllithium

Product 1

HCID 534652758-(2-Chloro-benzenesulfonyl)-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decane-1,7-dioneYield 31.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

2-(4-Trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decane-1,7-dione (0.105 g), product of example 1 step D), was dissolved in dry THF (10 ml), cooled to −78° C. under an argon atmosphere, treated dropwise with n-butyllithium (1.6 molar solution in hexanes, 0.22 ml) and then stirred for 20 minutes at −78° C. 2-Chlorobenzenesulfonyl chloride (0.074 g) in THF (2 ml) was then added dropwise, the mixture was stirred 15 minutes at −78° C., the cooling bath was removed and stirring was continued for further 75 minutes, allowing the temperature of the reaction mixture to rise to RT. The reaction mixture was then concentrated in vacuo, the residue adsorbed on silica gel and chromatographed on silica gel (AcOEt/heptane, gradient from 0 to 30%) to give the desired product (0.051 g) as an off-white solid. MS (ESI): 503.0 (MH−).

Workup

  1. stirringthe mixture was stirred 15 minutes at −78° C.
  2. customthe cooling bath was removed
  3. stirringstirring
  4. waitwas continued for further 75 minutes
  5. customto rise to RT
  6. concentrationThe reaction mixture was then concentrated in vacuo
  7. customthe residue adsorbed on silica gel and chromatographed on silica gel (AcOEt/heptane, gradient from 0 to 30%)

Sources & evidence

ORD record
ord-260d9b6221b444c2b188363bbb442e1e
Source dataset
uspto-grants-2012_01
Patent number
US08097634B2

Reaction notes

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