Water → HCID 59302360, compound

HRID 2237382Notes

Reaction equation

HRID 2237382 reaction equation
[C:1]([CH2:5][C@H:6]([C:8]([NH:10][C@H:11]([C:17]([OH:19])=[O:18])[CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:9])[NH2:7])([CH3:4])([CH3:3])[CH3:2].[OH2:20].CN1[CH2:27][CH2:26][O:25][CH2:24]C1>C1COCC1>[CH2:26]([O:25][C:24]([NH:7][C@@H:6]([C:8]([NH:10][C@H:11]([C:17]([OH:19])=[O:18])[CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:9])[CH2:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:20])[C:27]1[CH:8]=[CH:6][CH:5]=[CH:1][CH:2]=1

Participants

5

Reactant 3

HCID 962WaterHCID 79724-MethylmorpholineHCID 59302398HCID 59302398, compound

Product 1

HCID 59302360HCID 59302360, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-tert-Butyl-D-alanyl-3-tert-butyl-L-alanine (3.73 g, 12.1 mmol, example 92A) is dissolved in THF (170 ml) under an argon protective gas atmosphere. After the addition of water (170 ml), benzyloxycarbonyloxysuccinimide ester (4.52 g, 18.1 mmol, 1.5 equivalents) and N-methylmorpholine (4.28 g, 4.23 mmol, 3.5 equivalents) at 0° C., the mixture is stirred vigorously at RT until all starting material has been converted (several hours, HPLC monitoring, Method 2). The mixture is quenched with glacial acetic acid. The THF is drawn off in vacuo. The remaining aqueous phase is layered with ethyl acetate, adjusted to pH<3 with 4 N hydrochloric acid and then extracted several times with ethyl acetate. The organic phases are washed with brine, dried over sodium sulfate, filtered and concentrated. The resulting foam is stirred with acetonitrile, whereby a solid forms which is collected by filtration, then washed with a little acetonitrile. This process can be repeated several times more with the filtrate once it has been concentrated. The combined solids are dried under high vacuum whereby the title compound is obtained as a solid. The remaining mother liquor is concentrated and purified by means of preparative HPLC (Method 10). The title compound (combined solids and purification product from HPLC separation) is obtained as a solid (3.49 g, 71% of theory).

Workup

  1. custom(several hours, HPLC monitoring, Method 2)
  2. customThe mixture is quenched with glacial acetic acid
  3. extractionextracted several times with ethyl acetate
  4. washThe organic phases are washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. stirringThe resulting foam is stirred with acetonitrile, whereby a solid forms which
  9. filtrationis collected by filtration
  10. washwashed with a little acetonitrile
  11. concentrationhas been concentrated
  12. dry with materialThe combined solids are dried under high vacuum whereby the title compound
  13. customis obtained as a solid
  14. concentrationThe remaining mother liquor is concentrated
  15. custompurified by means of preparative HPLC (Method 10)

Sources & evidence

ORD record
ord-fb990a6ac16744ab854b015622c1b2c9
Source dataset
uspto-grants-2010_05
Patent number
US07718611B2

Reaction notes

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