tert-Butyl bromoacetate → (S)-N-[[3-[[(t-Butyloxy)carbonyl]amino]-2-oxo-1-azetidinyl]carbonyl]glycine, t-butyl ester

HRID 482921Notes

Reaction equation

HRID 482921 reaction equation
[O-:1][C:2]#[N:3].[K+].Br[CH2:6][C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[C:14]([O:18][C:19]([NH:21][C@H:22]1[CH2:25][NH:24][C:23]1=[O:26])=[O:20])([CH3:17])([CH3:16])[CH3:15]>CN(C)C=O>[C:14]([O:18][C:19]([NH:21][C@H:22]1[CH2:25][N:24]([C:2]([NH:3][CH2:6][C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[O:1])[C:23]1=[O:26])=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 11116749Tert-butyl N-[(3S)-2-oxoazetidin-3-yl]carbamateHCID 11378442Potassium cyanate

Product 1

HCID 131714544(S)-N-[[3-[[(t-Butyloxy)carbonyl]amino]-2-oxo-1-azetidinyl]carbonyl]glycine, t-butyl esterYield 26.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of potassium cyanate (186 mg, 2.3 mmol) in 2 ml of dimethylformamide was added t-butyl bromoacetate (0.356 ml, 2.2 mmol). The mixture was heated to 100° C. for 1 hour and cooled to room temperature. (3S)-3-[[(t-Butyloxy)carbonyl]amino]-2-azetidinone (372 mg, 2.0 mmol) was then added, and the mixture was heated from 65° C. to 140° C. over a period of 3.5 hours, finally maintaining the temperature at 140° C. for 0.5 hours. Upon cooling to room temperature, the crude product was extracted from ice cold 5% HCl with three portions of ethyl acetate. The combined organic layers were extracted twice with water and once with aqueous potassium bicarbonate. The organic layers were then dried over sodium sulfate and filtered through a pad of silica gel. The volatiles were removed, and the residue was subjected to chromatography on silica gel (eluting with 40% ethyl acetate-hexane) yielding 180 mg of the title compound.

Workup

  1. temperaturecooled to room temperature
  2. temperaturethe mixture was heated from 65° C. to 140° C. over a period of 3.5 hours
  3. temperaturefinally maintaining the temperature at 140° C. for 0.5 hours
  4. temperatureUpon cooling to room temperature
  5. extractionthe crude product was extracted from ice cold 5% HCl with three portions of ethyl acetate
  6. extractionThe combined organic layers were extracted twice with water and once with aqueous potassium bicarbonate
  7. dry with materialThe organic layers were then dried over sodium sulfate
  8. filtrationfiltered through a pad of silica gel
  9. customThe volatiles were removed

Sources & evidence

ORD record
ord-b27fa8184ac14f7e8574a6974d0ea759
Source dataset
uspto-grants-1986_03
Patent number
US04576749

Reaction notes

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