Morpholine → HCID 69736315, compound

HRID 1063218Notes

Reaction equation

HRID 1063218 reaction equation
CS(Cl)(=O)=O.[C:6]([O:10][C:11]([N:13]1[CH2:17][CH2:16][CH2:15][C@H:14]1[CH2:18]O)=[O:12])([CH3:9])([CH3:8])[CH3:7].C(N(CC)CC)C.[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>C(Cl)Cl.C1(C)C=CC=CC=1>[C:6]([O:10][C:11]([N:13]1[CH2:17][CH2:16][CH2:15][C@H:14]1[CH2:18][N:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1)=[O:12])([CH3:7])([CH3:8])[CH3:9]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 643448(S)-(-)-N-Boc-prolinol

Product 1

HCID 69736315HCID 69736315, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

Methanesulfonyl chloride (1.7 g, 14.9 mmol) was added dropwise to a solution of (S)-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (1.5 g, 7.45 mmol) and triethylamine (753 mg mg, 7.45 mmol) in CH2Cl2 at 0° C. After 3 h reaction mixture was concentrated to give a white solid. The resulting solid was suspended in toluene, morpholine (1.3 g, 14.9 mmol) was added, and the resulting mixture was heated to 110° C. in a sealed tube. After 12 h the reaction mixture was concentrated, the resulting residue was dissolved in EtOAc and water, the layers were separated, and the aqueous was further extracted with EtOAc. The combined organic extracts were dried over Na2SO4, and the material was purified on silica gel by flash column chromatography CH2Cl2/MeOH/NH4OH (98.5/1/0.5) to afford the title compound as a white solid (800 mg, 40%). MS: 271.2 (MH+); HPLC Rf: n.d.; HPLC purity: n.d.

Workup

  1. customAfter 3 h reaction mixture
  2. concentrationwas concentrated
  3. customto give a white solid
  4. concentrationAfter 12 h the reaction mixture was concentrated
  5. dissolutionthe resulting residue was dissolved in EtOAc
  6. customwater, the layers were separated
  7. extractionthe aqueous was further extracted with EtOAc
  8. dry with materialThe combined organic extracts were dried over Na2SO4
  9. customthe material was purified on silica gel by flash column chromatography CH2Cl2/MeOH/NH4OH (98.5/1/0.5)

Sources & evidence

ORD record
ord-867fd983e98547dc9f62cf8691769a0d
Source dataset
uspto-grants-2005_11
Patent number
US06964961B2

Reaction notes

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