Hydrochloric Acid → (S)-2-{(R)-2-Amino-4-[(R)-3-(cyclohexylmethyl-hydroxy-phosphinoyl)-2-hydroxy-propylcarbamoyl]-butyrylamino}-propionic acid

HRID 1926995Notes

Reaction equation

HRID 1926995 reaction equation
Cl.C([O:6][C:7](=[O:41])[C@@H:8]([NH:10][C:11](=[O:40])[C@H:12]([NH:32]C(OC(C)(C)C)=O)[CH2:13][CH2:14][C:15](=[O:31])[NH:16][CH2:17][C@@H:18]([OH:30])[CH2:19][P:20]([CH2:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)([OH:22])=[O:21])[CH3:9])(C)(C)C>O1CCOCC1.O>[NH2:32][C@H:12]([CH2:13][CH2:14][C:15](=[O:31])[NH:16][CH2:17][C@@H:18]([OH:30])[CH2:19][P:20]([CH2:23][CH:24]1[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]1)([OH:22])=[O:21])[C:11]([NH:10][C@@H:8]([CH3:9])[C:7]([OH:41])=[O:6])=[O:40]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 68621953(S)-2-{(R)-2-tert-butoxycarbonylamino-4-[(R)-3-(cyclohexylmethyl-hydroxy-phosphinoyl)-2-hydroxy-propylcarbamoyl]-butyrylamino}-propionic acid tert-butyl ester

Product 1

HCID 11647743(S)-2-{(R)-2-Amino-4-[(R)-3-(cyclohexylmethyl-hydroxy-phosphinoyl)-2-hydroxy-propylcarbamoyl]-butyrylamino}-propionic acidYield 37.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

4N HCl in dioxane (5 mL) was added to (S)-2-{(R)-2-tert-butoxycarbonylamino-4-[(R)-3-(cyclohexylmethyl-hydroxy-phosphinoyl)-2-hydroxy-propylcarbamoyl]-butyrylamino}-propionic acid tert-butyl ester (0.351 g, 0.592 mmol) in water (1 mL). The resulting colorless solution was stirred under N2 at rt overnight. The reaction mixture was concentrated in vacuo and the residue was purified by RP-HPLC eluting in a gradient of 10% CH3CN/H2O (adjusted with HCl pH=3.5) to 100% CH3CN over 20 min at 45 mL/min. The appropriate fractions were combined and lyophilized to give the title compound (0.096 g, 0.220 mmol) as a white solid. 1H NMR (CD3OD, 300 MHz): δ 4.38 (q, J=7.2 Hz, 1H), 4.04 (m, 1H), 3.90 (t, J=6.3 Hz, 1H), 3.35 (dd, J=5.7, 13.2 Hz, 1H), 3.21 (dd, J=5.7, 13.5 Hz, 1H), 2.41 (m, 2H), 2.11 (m, 2H), 1.92 (br d, 2H), 1.77-1.65 (m, 6H), 1.52 (dd, J=6.3, 13.5 Hz, 2H), 1.43 (d, J=7.2 Hz, 3H), 1.37-1.15 (m, 3H), 1.08-1.00 (m, 2H). 31P NMR (CD3OD, 300 MHz): δ 42.95. LCMS m/z: [M+H]+=436.25

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was purified by RP-HPLC
  3. washeluting in a gradient of 10% CH3CN/H2O (adjusted with HCl pH=3.5) to 100% CH3CN over 20 min at 45 mL/min

Sources & evidence

ORD record
ord-2cd6874bd006425f8b6b1eead0f1e1c0
Source dataset
uspto-grants-2012_05
Patent number
US08183231B2

Reaction notes

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