4-Methylmorpholine → HCID 69652473, compound

HRID 2215259Notes

Reaction equation

HRID 2215259 reaction equation
[C:1]([N:8](C1C=CC=CC=1O)[C@H:9]([C:12]([OH:14])=O)[CH2:10][SH:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCO[CH2:25][CH2:24]1.ClC(OCC)=O.[BH4-].[Na+].[O:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1>O>[C:4]([O:3][C:1]([NH:8][C@@H:9]([CH2:10][S:11][C:24]1[CH:25]=[CH:38][CH:39]=[CH:40][C:41]=1[OH:37])[CH2:12][OH:14])=[O:2])([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 8028TetrahydrofuranHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 21055309HCID 21055309, compound

Product 1

HCID 69652473HCID 69652473, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-10 °C

Procedure

74.45 g (0.237 mol) of N-Boc-(2-hydroxyphenyl)-L-cysteine (VIII) and 300 ml of distilled tetrahydrofuran are introduced into a round-bottomed flask kept under an inert atmosphere. The mixture is cooled to −10° C. and then 26 ml (0.236 mol) of N-methylmorpholine are added dropwise. After stirring for 15 minutes at −10° C., 22.7 ml (0.237 mol) of ethyl chloroformate are introduced dropwise. The mixture is stirred at −10° C. for 30 minutes and then the precipitate formed is filtered off under cold conditions. The filtrate is recovered directly in a round-bottomed flask and cooled to −10° C. 13.45 g (0.35 mol) of sodium borohydride in solution in 50 ml of water are then introduced in such a way that the temperature of the mixture does not exceed −10° C. At the end of the addition, the mixture is reheated to ambient temperature and stirred for 12 hours. The mixture is concentrated under reduced pressure, acidified using 250 ml of an aqueous potassium hydrogensulfate solution (2N) and extracted with dichloromethane. The combined organic phases are washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. 61.41 g (0.205 mol) of the title compound (IXa-1) are obtained in the form of a yellow oil, which is used without additional purification in the following stage.

Workup

  1. stirringThe mixture is stirred at −10° C. for 30 minutes
  2. customthe precipitate formed
  3. filtrationis filtered off under cold conditions
  4. customThe filtrate is recovered directly in a round-bottomed flask
  5. temperaturecooled to −10° C
  6. customdoes not exceed −10° C
  7. additionAt the end of the addition
  8. customis reheated to ambient temperature
  9. stirringstirred for 12 hours
  10. concentrationThe mixture is concentrated under reduced pressure
  11. extractionextracted with dichloromethane
  12. washThe combined organic phases are washed with brine
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0419cb12a3d1486ca2f6acdcf88bdcfe
Source dataset
uspto-grants-2006_09
Patent number
US07109234B2

Reaction notes

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