4-Methylmorpholine → HCID 72991582, compound

HRID 342252Notes

Reaction equation

HRID 342252 reaction equation
C[N:2]1[CH2:7][CH2:6][O:5][CH2:4]C1.[C:8]1(=[O:25])[N:12]([C@@H:13]([CH2:17][CH:18]=[CH2:19])[C:14]([OH:16])=O)[C:11](=[O:20])[C:10]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:9]12.S(=O)(=O)(O)[O-:27].[K+].[OH:32][C:33]1C2N=NNC=2[CH:36]=[CH:35][CH:34]=1>CN(C)C=O.C(Cl)Cl.C(OCC)(=O)C>[C:11]1(=[O:20])[N:12]([CH:13]([CH2:17][CH:18]=[CH2:19])[C:14]([NH:2][CH:7]([CH2:36][CH2:35][CH2:34][CH2:33][OH:32])[C:6]([O:5][CH3:4])=[O:27])=[O:16])[C:8](=[O:25])[C:9]2=[CH:24][CH:23]=[CH:22][CH:21]=[C:10]12

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 516920Potassium bisulfateHCID 11139382HCID 11139382, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 72991582HCID 72991582, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A slurry of (S)-2-amino-6-hydroxyhexanoic acid (2.42 g., 16.4 mmole) in dry methanol (60 ml.) was treated with gaseous hydrogen chloride until the mixture began to reflux. The homogeneous solution was then stirred at room temperature for 2.5 hours. The solvent was stripped and the residue azeotroped three times with toluene to give crude (S)-2-amino-6-hydroxyhexanoic acid, methyl ester, hydrochloride salt as an oil. This oil was dissolved in dimethylformamide (20 ml.) and methylene chloride (50 ml.) and treated with 4-methyl morpholine (3.20 ml., 2.94 g., 29.1 mmole). This mixture was cooled to 0° C. and treated with (S)-2-phthalimido-4-pentenoic acid [obtained from 7.0 g., 16.4 mmole of the salt product from part (a) by partitioning between 10% potassium bisulfate and ethyl acetate] in methylene chloride (10 ml.), followed by solid hydroxybenzotriazole (2.22 g., 16.4 mmole) and ethyl-3-(3-dimethylamino) propyl carbodiimide, hydrochloride salt (3.458 g., 18.0 mmole). After stirring at 0° C. for 0.5 hour and at room temperature for 2 hours, the reaction was partitioned between ethyl acetate and 0.5N hydrochloric acid. The ethyl acetate extract was washed successively with water, 50% saturated sodium bicarbonate, and brine, then dried (sodium sulfate), filtered and stripped. The residue was flash chromatographed (Merck silica gel, ethyl acetate) to give pure title compound as an oil which solidified upon standing. The solid was triturated with ethyl ether and hexane and collected by filtration to give 5.149 g. of analytically pure title product; m.p. 90°-92° C.; [α]D =+25.6 (c=1.1, chloroform). TLC (ethyl acetate) Rf =0.36.

Workup

  1. customthe reaction was partitioned between ethyl acetate and 0.5N hydrochloric acid
  2. extractionThe ethyl acetate extract
  3. washwas washed successively with water, 50% saturated sodium bicarbonate, and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customchromatographed (Merck silica gel, ethyl acetate)

Sources & evidence

ORD record
ord-ade148a54b614143bc9d5169ec31c6fb
Source dataset
uspto-grants-1999_01
Patent number
US05856477

Reaction notes

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