Triethylamine → 2-{3-[((S)-1-Dimethylaminomethyl-3,3-dimethyl-butylamino)-methyl]-benzyl}1,1-dioxo-1lambda6-isothiazolidine-3-carboxylic acid ethyl ester

HRID 1879475Notes

Reaction equation

HRID 1879475 reaction equation
Cl.[CH3:2][C:3]([CH3:12])([CH3:11])[CH2:4][C@H:5]([NH2:10])[CH2:6][N:7]([CH3:9])[CH3:8].C(N(CC)CC)C.[CH2:20]([O:22][C:23]([CH:25]1[CH2:29][CH2:28][S:27](=[O:31])(=[O:30])[N:26]1[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([CH:39]=O)[CH:34]=1)=[O:24])[CH3:21].C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[CH2:20]([O:22][C:23]([CH:25]1[CH2:29][CH2:28][S:27](=[O:31])(=[O:30])[N:26]1[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([CH2:39][NH:10][C@H:5]([CH2:6][N:7]([CH3:9])[CH3:8])[CH2:4][C:3]([CH3:12])([CH3:11])[CH3:2])[CH:34]=1)=[O:24])[CH3:21]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 582804492-(3-Formyl-benzyl)-1,1-dioxo-1lambda6 isothiazolidine-3-carboxylic acid ethyl esterHCID 86653800HCID 86653800, compound2×

Product 1

HCID 671532642-{3-[((S)-1-Dimethylaminomethyl-3,3-dimethyl-butylamino)-methyl]-benzyl}1,1-dioxo-1lambda6-isothiazolidine-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×

Procedure

To a stirred solution of (S)-4,4,N1,N1-tetramethyl-pentane-1,2-diamine hydrochloride salt (Intermediate 2, 0.921 g, 4.73 mmol) in methanol (10 mL) cooled in an ice bath (0° C.) was added triethylamine (2.19 mL, 15.7 mmol) and the solution was stirred at this temperature for 25 minutes. To this cooled solution was added 2-(3-formyl-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ethyl ester (0.937 g, 3.15 mmol) in methanol (35 mL) after which the solution was allowed to warm to room temperature and stirred for 2 hours. The solution was cooled to 0° C. and sodium cyanoborohydride (0.461 g, 7.3 mmol) and acetic acid (4 mL) were added and the solution was allowed to warm to room temperature and stirred overnight. The reaction was then concentrated under reduced pressure, partitioned between dichloromethane and saturated aqueous sodium bicarbonate and the layers were separated. The organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to provide crude 2-{3-[((S)-1-Dimethylaminomethyl-3,3-dimethyl-butylamino)-methyl]-benzyl}1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ethyl ester, which was carried on to the next step without further purification.

Workup

  1. stirringstirred for 2 hours
  2. temperatureThe solution was cooled to 0° C.
  3. temperatureto warm to room temperature
  4. stirringstirred overnight
  5. concentrationThe reaction was then concentrated under reduced pressure
  6. custompartitioned between dichloromethane and saturated aqueous sodium bicarbonate
  7. customthe layers were separated
  8. washThe organic phase was washed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4ae0ca04805545bcb2ec4a7b8d1ad89d
Source dataset
uspto-grants-2012_11
Patent number
US08314250B2

Reaction notes

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