4-Methylmorpholine → (S)-tert-butyl 1-cyclohexyl-4-diazo-3-oxobutan-2-ylcarbamate

HRID 253557Notes

Reaction equation

HRID 253557 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[N+:35](=[CH2:37])=[N-:36]>C1COCC1.CCOCC.C(O)(=O)C>[CH:14]1([CH2:13][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:10](=[O:12])[CH:37]=[N+:35]=[N-:36])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 9550DiazomethaneHCID 62365Isobutyl chloroformateHCID 10588189(2S)-2-(((tert-butoxy)carbonyl)amino)-3-cyclohexylpropanoic acid

Product 1

HCID 86632797(S)-tert-butyl 1-cyclohexyl-4-diazo-3-oxobutan-2-ylcarbamateYield 100%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of (S)-2-(tert-butoxycarbonylamino)-3-cyclohexylpropanoic acid (37 g, 0.136 mmol) in anhydrous THF (300 mL) cooled to −20° C. was added dropwise N-methylmorpholine (16.6 mL, 0.15 mmol), followed by isobutyl chloroformate (20 mL, 0.15 mmol) and the reaction mixture was stirred at −20° C. for 30 min. The mixture was warmed to 0° C., and an etheral solution of CH2N2 (0.8 mol) was added. Stirring was continued overnight at rt. Excess diazomethane was decomposed by addition of acetic acid. The mixture was diluted with ether, washed with brine, satd aq NaHCO3 and brine to give a solution of crude (S)-tert-butyl 1-cyclohexyl-4-diazo-3-oxobutan-2-ylcarbamate (48 g, 100%), which was used without isolation.

Workup

  1. temperatureThe mixture was warmed to 0° C.
  2. stirringStirring
  3. waitwas continued overnight at rt
  4. washwashed with brine

Sources & evidence

ORD record
ord-e9d75f9b4f0e4c12b3fa8eb57c61ea24
Source dataset
uspto-grants-2011_01
Patent number
US07872028B2

Reaction notes

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