Potassium Hydroxide → HCID 131721919, compound

HRID 2269598Notes

Reaction equation

HRID 2269598 reaction equation
[NH:1]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:2][C:3]([N:5]1[CH2:22][CH2:21][CH2:20][C@H:6]1[C:7]([NH:9][C@H:10]([C:15]([O:17]CC)=[O:16])[CH2:11][CH2:12][CH2:13][CH3:14])=[O:8])=[O:4].[OH-].[K+]>C1COCC1.[H][H]>[NH:1]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:2][C:3]([N:5]1[CH2:22][CH2:21][CH2:20][C@H:6]1[C:7]([NH:9][C@H:10]([C:15]([OH:17])=[O:16])[CH2:11][CH2:12][CH2:13][CH3:14])=[O:8])=[O:4]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 131721918HCID 131721918, compound

Product 1

HCID 131721919HCID 131721919, compound

Reagents, catalysts & solvents 1

HCID 178420693HCID 178420693, compoundSolvent

Conditions

Temperature
0 °C

Procedure

Boc-Gly-Pro-Nleu-OEt (4.3 g, 0.0104 mol.) was dissolved in 80 ml THF/H2) (v/v, 1:1) and the solution was chilled to 0° C. on a water-ice bath. KOH (1.1 g dissolved in 20 ml H2O) was added while stirring the solution. After a while, the bath was removed and the stirring was continued for one more hour. The THF was removed under reduced pressure. The aqueous solution was extracted by ethyl acetate 2×50 ml. Then, the aqueous layer was chilled to 0° C. and was acidified to about pH=3 by addition of concentrated HCl while swirling the solution vigorously at the same time (the aqueous layer was covered by 50 ml ethyl acetate). The product was extracted from the aqueous layer by ethyl acetate 3×50 ml. The organic layer was combined and dried by Na2SO4. The ethyl acetate was removed under reduced pressure. Column chromatography (E/H:5:2) was carried out to obtain the pure product (white solid, 3.6 g, 92%). TLC Rf=0.44 (developing solvents: CMA, 85:15:3). FAB-MS, observed (M+H)+=386. Analytical RP-HPLC chromatogram, single peak, retention time RT=13 min. (25-60% B in 30 min.). 1H-NMR (500 MHz, DMSO-d6, 25° C., assignment by TOCSY) δ12.50 (s, 1H, carboxyl), 6.62 (m, 1H, Gly-NH), 4.92 (d, Pro-α), 4.72 (d, Pro-α), 4.56 (d, Nleu-α), 4.48 (d, Pro-α), 4.12 (m, Nleu-α), 4.00-3.90 (m, Nleu-α), 3.83-3.66 (m, Nleu-α, Gly-α), 3.64-3.50 (m, Gly-α, Nleu-α), 3.50-3.33 (m, Pro-δ), 2.34-1.60 (sets of bands, Pro-β, Pro-γ, Nleu-γ), 1.38 (s, 9H, Boc-CH3), 0.88 (dd, Nleu-δ), 0.75 (dd, Nleu-δ).

Workup

  1. customAfter a while, the bath was removed
  2. customThe THF was removed under reduced pressure
  3. extractionThe aqueous solution was extracted by ethyl acetate 2×50 ml
  4. temperatureThen, the aqueous layer was chilled to 0° C.
  5. additionwas acidified to about pH=3 by addition of concentrated HCl
  6. extractionThe product was extracted from the aqueous layer by ethyl acetate 3×50 ml
  7. dry with materialdried by Na2SO4
  8. customThe ethyl acetate was removed under reduced pressure
  9. customto obtain the pure product (white solid, 3.6 g, 92%)
  10. customAnalytical RP-HPLC chromatogram, single peak, retention time RT=13 min. (25-60% B in 30 min.)

Sources & evidence

ORD record
ord-0fcab474f8674cd988bfb34941a1c47b
Source dataset
uspto-grants-2001_12
Patent number
US06329506B1

Reaction notes

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