Dimethyl Sulfoxide → (R)-2-Methyl-5-oxo-4-(3-oxo-propyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester

HRID 655563Notes

Reaction equation

HRID 655563 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16]([N:18]1[CH2:24][CH2:23][C:22](=[O:25])[N:21]([CH2:26][CH2:27][CH2:28][OH:29])[CH2:20][C@H:19]1[CH3:30])=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C.P([O-])(O)(O)=O.[K+]>ClCCl>[C:11]([O:15][C:16]([N:18]1[CH2:24][CH2:23][C:22](=[O:25])[N:21]([CH2:26][CH2:27][CH:28]=[O:29])[CH2:20][C@H:19]1[CH3:30])=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516951Monobasic potassium phosphateHCID 67080704(R)-4-(3-Hydroxy-propyl)-2-methyl-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester

Product 1

HCID 86638114(R)-2-Methyl-5-oxo-4-(3-oxo-propyl)-[1,4]diazepane-1-carboxylic acid tert-butyl esterYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-6 °C

Procedure

To a solution of 0.161 ml (1.84 mmol, 1.15 eq.) of oxalyl chloride in 9 ml dichloro-methane at −50 to −60° C. was added a solution of 0.272 ml (3.83 mmol, 2.4 eq.) dimethyl-sulfoxide in 1.5 ml dichloromethane within 5 min. The solution was stirred for 5 min and a solution of 0.457 g (1.60 mmol) of (R)-4-(3-hydroxy-propyl)-2-methyl-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester (example 1B) in 4.5 ml dichloromethane was added within 5 min. The mixture was stirred for 15 min and 1.11 ml (7.98 mmol, 5 eq.) of triethylamine was added within 5 min. The suspension was stirred for 3.5 h and slowly warmed to −6° C. The reaction was neutralized with cold 10% aq. potassium dihydrogenphosphate solution (adjusted with solid potassium dihydrogenphosphate to pH 4-5) and extracted with ethyl acetate (3 times). The organic phases were washed with fresh sat. aq. sodium hydrogencarbonate solution and 10% aq. sodium chloride solution, dried over Na2SO4 and evaporated to give 0.418 g (92%) of the title compound as colorless oil. MS: 285.1 (MH+).

Workup

  1. stirringThe mixture was stirred for 15 min
  2. stirringThe suspension was stirred for 3.5 h
  3. extractionextracted with ethyl acetate (3 times)
  4. washThe organic phases were washed with fresh sat. aq. sodium hydrogencarbonate solution and 10% aq. sodium chloride solution
  5. dry with materialdried over Na2SO4
  6. customevaporated

Sources & evidence

ORD record
ord-6a2aa55fda774687a2dc2c0f4701a4b5
Source dataset
uspto-grants-2011_12
Patent number
US08071586B2

Reaction notes

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