Acetic Acid → Tert-butyl 4-cyclobutyl-1,4-diazepane-1-carboxylate

HRID 2361631Notes

Reaction equation

HRID 2361631 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15]1(=O)[CH2:18][CH2:17][CH2:16]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[CH:15]1([N:11]2[CH2:12][CH2:13][CH2:14][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]2)[CH2:18][CH2:17][CH2:16]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14496CyclobutanoneHCID 516892Sodium BicarbonateHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 57425297Tert-butyl 4-cyclobutyl-1,4-diazepane-1-carboxylateYield 96%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
22.5 °C

Procedure

To a stirred solution of [1,4]diazepane-1-carboxylic acid tert-butyl ester (5 g, 24.97 mmol) in DCE (70 ml) at 20 to 25° C. was added cyclobutanone (1.75 g, 24.97 mmol) followed by acetic acid (1.5 g, 24.97 mmol) dropwise. The resulting mixture was stirred at 20 to 25° C. for ca. 2 h. Sodium triacetoxyborohydride (7.94 g, 37.46 mmol) was added in 9 portions, keeping the temperature in the range of 20 to 25° C. The resulting suspension was stirred at 20 to 25° C. overnight. Saturated NaHCO3 (80 ml) was added in four portions and the biphasic mixture stirred at 20 to 25° C. for ca. ½ h. The organic layer was separated, washed with water (20 ml) and the aqueous phase back extracted at pH 9 with DCM (20 ml). The combined organic phases were dried (Na2SO4), filtered and concentrated in vacuo to provide the title compound as yellow oil (6.1 g, 96%).

Workup

  1. customin the range of 20 to 25° C
  2. stirringThe resulting suspension was stirred at 20 to 25° C. overnight
  3. stirringthe biphasic mixture stirred at 20 to 25° C. for ca. ½ h
  4. customThe organic layer was separated
  5. washwashed with water (20 ml)
  6. extractionthe aqueous phase back extracted at pH 9 with DCM (20 ml)
  7. dry with materialThe combined organic phases were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a0caf140d037433cbf79edb894b9aefb
Source dataset
uspto-grants-2014_04
Patent number
US08691804B2

Reaction notes

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