1-Bromo-2-Chloroethane → HCID 66817946, compound

HRID 1755069Notes

Reaction equation

HRID 1755069 reaction equation
C([Li])CCC.[C:6]([O:10][C:11](=[O:37])[N:12]([C:14]1[CH:19]=[C:18]([CH3:20])[C:17]([CH2:21][CH2:22][S:23]([N:26]2[CH2:35][CH2:34][C:29]3([O:33][CH2:32][CH2:31][O:30]3)[CH2:28][CH2:27]2)(=[O:25])=[O:24])=[C:16]([CH3:36])[CH:15]=1)[CH3:13])([CH3:9])([CH3:8])[CH3:7].Br[CH2:39][CH2:40][Cl:41].[Cl-].[NH4+]>C1COCC1>[C:6]([O:10][C:11](=[O:37])[N:12]([C:14]1[CH:19]=[C:18]([CH3:20])[C:17]([CH2:21][CH:22]([S:23]([N:26]2[CH2:27][CH2:28][C:29]3([O:33][CH2:32][CH2:31][O:30]3)[CH2:34][CH2:35]2)(=[O:24])=[O:25])[CH2:39][CH2:40][Cl:41])=[C:16]([CH3:36])[CH:15]=1)[CH3:13])([CH3:9])([CH3:8])[CH3:7]

Participants

6

Reactant 4

HCID 78491-Bromo-2-ChloroethaneHCID 25517Ammonium ChlorideHCID 66818607HCID 66818607, compoundHCID 178418339Butyllithium

Product 1

HCID 66817946HCID 66817946, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

n-Butyllithium (1.6 M solution in hexane, 0.58 ml, 0.93 mmol) was added to a solution of {4-[2-(1,4-dioxa-8-aza-spiro[4.5]decane-8-sulfonyl)-ethyl]-3,5-dimethyl-phenyl}-methyl-carbamic acid tert-butyl ester (195.7 mg, 0.4176 mmol) in THF (4.2 ml) at −78° C. over six minutes, and the mixture was stirred at the same temperature for 20 minutes. 1-Bromo-2-chloro-ethane (105 μl, 1.26 mmol) was added to the reaction solution at −78° C. within 10 minutes. The mixture was then stirred while warming from −78° C. to 0° C. over one hour, and further stirred at room temperature for one hour. A 50% saturated aqueous ammonium chloride solution was added, followed by extraction with ethyl acetate. The organic layer was then dried over MgSO4 and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/2) to give {4-[4-chloro-2-(1,4-dioxa-8-aza-spiro[4.5]decane-8-sulfonyl)-butyl]-3,5-dimethyl-phenyl}-methyl-carbamic acid tert-butyl ester (133 mg, 60%).

Workup

  1. stirringThe mixture was then stirred
  2. temperaturewhile warming from −78° C. to 0° C. over one hour
  3. stirringfurther stirred at room temperature for one hour
  4. extractionfollowed by extraction with ethyl acetate
  5. dry with materialThe organic layer was then dried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/2)

Sources & evidence

ORD record
ord-9ddce01795af496a84bf41f8dd4820a9
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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