4-Methylmorpholine → HCID 86749261, compound

HRID 2396478Notes

Reaction equation

HRID 2396478 reaction equation
[CH3:1][C:2]([CH3:27])([O:4][C:5]([NH:7][C@H:8]([C:24]([OH:26])=O)[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:12][CH:11]=1)=[O:6])[CH3:3].ClC(OCC(C)C)=O.CN1CCOCC1.[CH3:43][N:44]([N:51]=O)C(N[N+]([O-])=O)=N>O1CCCC1>[N+:44](=[CH:43][C:24](=[O:26])[C@@H:8]([NH:7][C:5](=[O:6])[O:4][C:2]([CH3:1])([CH3:27])[CH3:3])[CH2:9][C:10]1[CH:11]=[CH:12][C:13]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:14][CH:15]=1)=[N-:51]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 98763O-benzyl-N-((tert-butoxy)carbonyl)-L-tyrosineHCID 135436526N-Methyl-N'-nitro-N-nitrosoguanidine

Product 1

HCID 86749261HCID 86749261, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-5 °C

Procedure

To a solution of N-[(1,1-dimethylethoxy)carbonyl]--O-benzyl-L-tyrosine in dry tetrahydrofuran (90 ml) cooled at -20° C. to -25° C. was added isobutyl chloroformate (8.7 ml, 67.3 mmol) followed by 4-methylmorpholine (6.8 ml, 67.3 mmol) and the mixture was stirred for 20 minutes. The precipitate was filtered and washed with dry tetrahydrofuran. The filtrate was cooled to -5° C. and poured into a diazomethane in ether solution (prepared from 1-methyl-3-nitro-1-nitrosoguanidine (29.7 g, 202 mmol) as described in Example 1 (d) at 0° C. The resulting yellow solution was kept at 0° C. for 2.0 hours, then at room temperature overnight. Nitrogen was then bubbled through the solution for 30 minutes, the solution diluted with ethyl ether (500 ml) and then washed with water, saturated sodium bicarbonate, and brine, and dried over magnesium sulfate. Concentration in vacuo afforded a yellow residue which was triturated with hexane (500 ml) to give 24.5 g of (S)-[3-diazo-2-oxo-1-[[4-(phenylmethoxy)phenyl]methyl]propyl]carbamic acid, 1,1-dimethylethyl ester.

Workup

  1. filtrationThe precipitate was filtered
  2. washwashed with dry tetrahydrofuran
  3. additionpoured into a diazomethane in ether solution (
  4. waitThe resulting yellow solution was kept at 0° C. for 2.0 hours
  5. customat room temperature
  6. customovernight
  7. customNitrogen was then bubbled through the solution for 30 minutes
  8. additionthe solution diluted with ethyl ether (500 ml)
  9. washwashed with water, saturated sodium bicarbonate, and brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationConcentration in vacuo
  12. customafforded a yellow residue which
  13. customwas triturated with hexane (500 ml)

Sources & evidence

ORD record
ord-afb6ab0452794a5da4acbe2cca5db71b
Source dataset
uspto-grants-1996_02
Patent number
US05492910

Reaction notes

Loading…