4-Methylmorpholine → HCID 11674407, compound

HRID 1833329Notes

Reaction equation

HRID 1833329 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:18][CH2:17][CH2:16][C@H:12]1[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.C(OC(Cl)=O)C(C)C.Cl.[CH3:35][O:36][C:37](=[O:41])[CH2:38][CH2:39][NH2:40]>CN(C)C=O>[CH3:35][O:36][C:37](=[O:41])[CH2:38][CH2:39][NH:40][C:13](=[O:15])[C@@H:12]1[CH2:16][CH2:17][CH2:18][N:11]1[C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 101987Benzyloxycarbonyl-L-prolineHCID 2734767Methyl 3-aminopropanoate hydrochloride

Product 1

HCID 11674407HCID 11674407, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-20 °C

Procedure

24.9 g of benzyloxycarbonyl-L-proline were dissolved in 200 ml of dimethylformamide, cooled to -20° C and treated with 11.1 ml of N-methylmorpholine and 13.0 ml of chloroformic acid isobutyl ester. The suspension was stirred for a further 2 minutes at -° C and then treated with a suspension, pre-cooled to -20° C, prepared from 14.0 g of β-alanine methyl ester hydrochloride and 11.1 ml of N-methylmorpholine in 100 ml of dimethylformamide. The mixture was stirred for 30 minutes at a temperature below -10° C and for a further 30 minutes at room temperature, filtered and the filtrate concentrated in vacuo. The oily residue was dissolved in 1.2 liters of ethyl acetate and washed three times, each time with 1-N hydrochloric acid, water, 10% sodium carbonate solution and saturated sodium chloride solution, and dried over sodium sulphate. The organic phase was concentrated in vacuo and the oily residue crystallised from ethyl acetate/hexane. Yield: 22.8 g; melting point 55° C; [α]D25 = -50.7° (c = 1 in methanol).

Workup

  1. additiontreated with a suspension
  2. temperaturepre-cooled to -20° C
  3. stirringThe mixture was stirred for 30 minutes at a temperature below -10° C and for a further 30 minutes at room temperature
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated in vacuo
  6. dissolutionThe oily residue was dissolved in 1.2 liters of ethyl acetate
  7. washwashed three times
  8. dry with materialeach time with 1-N hydrochloric acid, water, 10% sodium carbonate solution and saturated sodium chloride solution, and dried over sodium sulphate
  9. concentrationThe organic phase was concentrated in vacuo
  10. customthe oily residue crystallised from ethyl acetate/hexane

Sources & evidence

ORD record
ord-8f21039cc8684dc5bbd44705be01baf5
Source dataset
uspto-grants-1978_01
Patent number
US04066635

Reaction notes

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