Hydrochloric Acid → (-)-3(S)-(2-(R)-Amino-3-phenylpropionylamino)-5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

HRID 2379359Notes

Reaction equation

HRID 2379359 reaction equation
C(OC([NH:8][C@H:9]([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:10]([NH:12][CH:13]1[N:19]=[C:18]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[C:17]2[CH:26]=[CH:27][CH:28]=[CH:29][C:16]=2[N:15]([CH3:30])[C:14]1=[O:31])=[O:11])=O)(C)(C)C.Cl>C(OCC)(=O)C>[NH2:8][C@H:9]([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:10]([NH:12][C@H:13]1[N:19]=[C:18]([CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]2)[C:17]2[CH:26]=[CH:27][CH:28]=[CH:29][C:16]=2[N:15]([CH3:30])[C:14]1=[O:31])=[O:11]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 1317187683(R,S)-[2(R)-(tert-Butyloxycarbonvl)amino-3-phenylpropionylamino]-5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

Product 1

HCID 18656031(-)-3(S)-(2-(R)-Amino-3-phenylpropionylamino)-5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-oneYield 20%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

3(R,S)-[2(R)-(tert-Butyloxycarbonyl)amino-3-phenylpropionylamino]- 5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (12.7 g, 24.5 mmol) [Example 27, Step 2] was dissolved in ethyl acetate (20 ml) and cooled to 0° C. This solution was then saturated with hydrogen chloride gas. After 1.5 h the resulting precipitate was collected by filtration. After recrystallisation twice from ethanol, the precipitate was partitioned between ethyl acetate (50 ml) and 10% sodium carbonate solution (50 ml). The organic phase was separated and the aqueous extracted with further ethyl acetate (2×50 ml). The combined organic phases were dried (Na2SO4) and evaporated in vacuo to afford the title compound (2 g, 20%) as a pale yellow solid. mp 75°-78° C. 1H NMR (360 MHz, CDCl3) δ 1.03-1.41 (4H, m), 1.48-1.72 (4H, m), 1.82-1.92 (1H, m), 1.97-2.06 (1H, m), 2.70-2.84 (2H, m), 3.28-3.42 (4H, m), 3.76-3.82 (1H, m), 5.36 (1H, d, J=8.2 Hz), 7.21-7.33 (7H, m), 7.50 (1H, t, J=8.4 Hz), 7.56 (1H, d, J=8.1 Hz), 8.67-8.72 (1H, m). [α]D -13.5° (c=0.63, CH3OH).

Workup

  1. filtrationAfter 1.5 h the resulting precipitate was collected by filtration
  2. customAfter recrystallisation twice from ethanol
  3. customthe precipitate was partitioned between ethyl acetate (50 ml) and 10% sodium carbonate solution (50 ml)
  4. customThe organic phase was separated
  5. extractionthe aqueous extracted with further ethyl acetate (2×50 ml)
  6. dry with materialThe combined organic phases were dried (Na2SO4)
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-22a7c4c9203b447aab8a1082808c4e36
Source dataset
uspto-grants-1994_11
Patent number
US05360802

Reaction notes

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