4-Chlorobenzenesulfonyl chloride → HCID 71554977, compound

HRID 2281674Notes

Reaction equation

HRID 2281674 reaction equation
[Cl:1][C:2]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:3]=1[CH2:4][NH:5][C:6]([N:8]1[C:11]2([CH2:14][NH:13][CH2:12]2)[CH2:10][CH2:9]1)=[O:7].C(N(CC)CC)C.[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([S:34](Cl)(=[O:36])=[O:35])=[CH:30][CH:29]=1>ClCCl>[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([S:34]([N:13]2[CH2:12][C:11]3([N:8]([C:6]([NH:5][CH2:4][C:3]4[CH:15]=[CH:16][C:17]([Cl:19])=[CH:18][C:2]=4[Cl:1])=[O:7])[CH2:9][CH2:10]3)[CH2:14]2)(=[O:36])=[O:35])=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 73984-Chlorobenzenesulfonyl chlorideHCID 8471TriethylamineHCID 86682350HCID 86682350, compound

Product 1

HCID 71554977HCID 71554977, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl 1-(2,4-dichlorobenzylcarbamoyl)-1,6-diazaspiro[3.3]heptane-6-carboxylate (440 mg, 1.10 mmol) in dichloromethane (7 mL) was added TFA (593 μl, 7.7 mmol). After being stirred 2 h at ambient temperature, the reaction mixture was concentrated under reduced pressure. The residue was partitioned in toluene (10 mL) and then concentrated; this procedure was repeated twice to give the free amine (468 mg), which was used without further purification in the next step. To a solution of the previously obtained N-(2,4-dichlorobenzyl)-1,6-diazaspiro[3.3]heptane-1-carboxamide in dichloromethane (12 mL) was added at 0° C. triethylamine (217 μl, 1.56 mmol) followed by 4-chlorobenzene-1-sulfonyl chloride (329 mg, 1.56 mmol). The reaction mixture was left to warm to ambient temperature overnight, and was then diluted with dichloromethane (10 mL) and quenched with water (10 mL). The aqueous phase was extracted with dichloromethane and the combined organic phases were washed with brine, dried over sodium sulfate and were concentrated under reduced pressure. Purification by chromatography (SiO2; heptane:ethyl acetate 1:4) afforded the title compound (445 mg, 85%) as a colorless solid. HRMS (EI): 473.0134 (exact mass calculated for C19H18Cl3N3O3S ([M]+)=473.0134).

Workup

  1. customwas used without further purification in the next step
  2. waitThe reaction mixture was left
  3. customquenched with water (10 mL)
  4. extractionThe aqueous phase was extracted with dichloromethane
  5. washthe combined organic phases were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationwere concentrated under reduced pressure
  8. customPurification by chromatography (SiO2; heptane:ethyl acetate 1:4)

Sources & evidence

ORD record
ord-522e0573b42546b3947c0bc75a07adbf
Source dataset
uspto-grants-2015_09
Patent number
US09139593B2

Reaction notes

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