4-Methylmorpholine → (5R)-1-{(2S)-2-((tert-butoxycarbonyl)amino)-2-cyclopentylethanoyl}-5-ethynyl-L-prolinamide

HRID 1293344Notes

Reaction equation

HRID 1293344 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1)[C:10]([N:12]1[C@@H:19]([C:20]#[CH:21])[CH2:18][CH2:17][C@H:13]1[C:14]([OH:16])=O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N:28]1CCOCC1.C(OC(Cl)=O)C(C)C.O1CCOCC1.OS([O-])(=O)=O.[K+]>C1COCC1.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1)[C:10]([N:12]1[C@@H:19]([C:20]#[CH:21])[CH2:18][CH2:17][C@H:13]1[C:14]([NH2:28])=[O:16])=[O:11])=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 312751,4-DioxaneHCID 62365Isobutyl chloroformateHCID 516920Potassium bisulfateHCID 86592934(5R)-1-{(2S)-2-((tert-butoxycarbonyl)amino)-2-cyclopentylethanoyl}-5-ethynyl-L-proline

Product 1

HCID 86592935(5R)-1-{(2S)-2-((tert-butoxycarbonyl)amino)-2-cyclopentylethanoyl}-5-ethynyl-L-prolinamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

To a stirred solution of (5R)1-{(2S)-2-((tert-butoxycarbonyl)amino)-2-cyclopentylethanoyl}-5-ethynyl-L-proline (1.28 g, 3.38 mmol ) in THF (25 mL) at −15° C. under nitrogen, was added 4-methylmorpholine (0.44 mL, 4.05 mmol), and isobutylchloroformate (0.5 mL, 3.72 mmol) over 2 minutes. The reaction mixture was stirred at −15° C. under nitrogen for 30 minutes, and a solution of 0.5 MNH3 in dioxane (34 mL, 16.90 mmol ) was added. The reaction mixture diluted with water, the pH adjusted to 4 by the addition of 4% KHSO4 and extracted with ethyl acetate (3×). The combined extracts were washed with brine, dried (Na2SO4), filtered and evaporated. The residue was purified by flash column chromatography (5% MeOH/CH2Cl2) to provide the titled compound. MS (CI) m/e 364 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washThe combined extracts were washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by flash column chromatography (5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-3d9bb01fb90943b7aa5bf059d6773e70
Source dataset
uspto-grants-2007_07
Patent number
US07238724B2

Reaction notes

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