Tetrahydrofuran → (3S)-3-[(8,8-dimethyl-4,4-dioxo-7-oxa-4lambda6-thia-5-azaspiro[2.5]oct-5-en-6-yl)amino]-3-phenylpropan-1-ol

HRID 72353Notes

Reaction equation

HRID 72353 reaction equation
[OH:1][C:2]([C:5]1([S:8]([NH2:11])(=[O:10])=[O:9])[CH2:7][CH2:6]1)([CH3:4])[CH3:3].[CH3:12][Si]([N-][Si](C)(C)C)(C)C.[Na+].[N-:22]=[C:23]=S.BrN1[C:30](=O)[CH2:29][CH2:28][C:27]1=O.[CH2:33]1[CH2:37][O:36][CH2:35][CH2:34]1>CN1C(=O)CCC1.O>[CH3:3][C:2]1([CH3:4])[C:5]2([CH2:6][CH2:7]2)[S:8](=[O:9])(=[O:10])[N:11]=[C:23]([NH:22][C@H:33]([C:37]2[CH:12]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:34][CH2:35][OH:36])[O:1]1

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 67184N-bromobutanimideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 692665221-(1-Hydroxy-1-methylethyl)cyclopropanesulfonamideHCID 178418790HCID 178418790, compound

Product 1

HCID 178431667(3S)-3-[(8,8-dimethyl-4,4-dioxo-7-oxa-4lambda6-thia-5-azaspiro[2.5]oct-5-en-6-yl)amino]-3-phenylpropan-1-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

250 mg of 1-(1-hydroxy-1-methyl-ethyl)cyclopropanesulfonamide were dissolved in 2 ml of NMP, and admixed while cooling with ice with 0.70 ml of a 2 N solution of sodium bis(trimethylsilyl)amide in THF and, after stirring for 5 minutes, with the isothiocyanate solution prepared above. After stirring for 1.5 hours, 248 mg of N-bromosuccinimide were added and the resulting reaction solution was stirred again for 10 minutes. The reaction mixture was added to 20 ml of water and extracted three times with 20 ml of ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over Na2SO4 and concentrated by rotary evaporation. The residue was dissolved in 5 ml of methanol, 0.20 ml of concentrated hydrochloric acid was added and the mixture was stirred for 1.5 hours. After the addition of 1.26 ml of 1 N aqueous sodium hydroxide solution, the mixture was concentrated by rotary evaporation and purified in a purification laboratory by means of preparative HPLC. After lyophilization of the product-containing fractions, the product (26 mg) was thus obtained with a molecular weight of 338.4 g/mol (C16H22N2O4S); MS (ESI): m/e=339 (M+H+).

Workup

  1. customprepared above
  2. customthe resulting reaction solution
  3. stirringwas stirred again for 10 minutes
  4. extractionextracted three times with 20 ml of ethyl acetate
  5. washThe combined organic phases were washed with saturated aqueous sodium chloride solution
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated by rotary evaporation
  8. dissolutionThe residue was dissolved in 5 ml of methanol
  9. addition0.20 ml of concentrated hydrochloric acid was added
  10. stirringthe mixture was stirred for 1.5 hours
  11. additionAfter the addition of 1.26 ml of 1 N aqueous sodium hydroxide solution
  12. concentrationthe mixture was concentrated by rotary evaporation
  13. custompurified in a purification laboratory by means of preparative HPLC

Sources & evidence

ORD record
ord-254f3308bad542328aecd75a3820e1db
Source dataset
uspto-grants-2014_09
Patent number
US08828994B2

Reaction notes

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