Hydrochloric Acid → HCID 13755878, compound

HRID 980330Notes

Reaction equation

HRID 980330 reaction equation
CC(C)(OC([NH:7][C@@H:8]([CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[CH:9]([S:35]CC1C=CC(OC)=CC=1)[CH2:10][NH:11][C@H:12]([C:20]([NH:22][C@H:23]([C:28]([O:30]C(C)(C)C)=[O:29])[CH2:24][CH:25]([CH3:27])[CH3:26])=[O:21])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=O)C.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O.Cl>O>[NH2:7][CH:8]([CH2:45][C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)[CH:9]([SH:35])[CH2:10][NH:11][C@H:12]([C:20]([NH:22][C@H:23]([C:28]([OH:30])=[O:29])[CH2:24][CH:25]([CH3:27])[CH3:26])=[O:21])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 13755876HCID 13755876, compound

Product 1

HCID 13755878HCID 13755878, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N-[N-[(3S)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-2-[[(4-methoxyphenyl)methyl]thio]-4-phenylbutyl]-L-phenylalanyl]-L-leucine, 1,1-dimethylethyl ester (780 mg, 1.06 mmol), anisole (1.0 ml) and trifluoroacetic acid (14 ml) was stirred at room temperature under argon. After 1 hour, the reaction was cooled to 0° C. and mercuric trifluoroacetate (497 mg, 1.1 eq) was added. The reaction was stirred for 1 hour at 0° C. and then concentrated to a red oil. The oil was triturated with ether/hexane and a nearly colorless solid was collected and washed with hexane. The solid was dissolved in degassed 80% aqueous acetic acid (20 ml) and hydrogen sulfide was bubbled through the solution for 30 minutes. The black reaction mixture was filtered through a pad of Celite followed by a Millipore filter (Teflon). The filtrate was concentrated to an amber oil. The oil was diluted with degassed double distilled water (20 ml) and 1N hydrochloric acid (3.2 ml, 1.5 eq) and the mixture filtered (Millipore, Metricel). The clear, colorless filtrate was lyophilized and relyophilized twice from water to yield the title compound as a fluffy, colorless solid: 490 mg (0.87 mmol); Rf =0.70 (silica gel, N-butanol:water:acetic acid, 4:1:1); Rf =0.75 (silica gel, chloroform:methanol:acetic acid, 4:1:1); fast atom bombardment mass spectrum: (M+H)+ m/e=458, (M-H)- m/e=456; melting point 123°-160° C.; [α]D =-12.8° (c=1.23, methanol). Analysis: C25H35N3O3S.1.8 mole HCl.2.2 mole H2O: C, 53.34; H, 7.38; N, 7.46; S, 5.69; SH 5.87; Cl, 11.33. Found: C, 53.06; H, 7.15; N, 7.12; S, 5.39; SH, 5.86; Cl, 11.08.

Workup

  1. concentrationconcentrated to a red oil
  2. customThe oil was triturated with ether/hexane
  3. customa nearly colorless solid was collected
  4. washwashed with hexane
  5. dissolutionThe solid was dissolved in degassed 80% aqueous acetic acid (20 ml) and hydrogen sulfide
  6. customwas bubbled through the solution for 30 minutes
  7. customThe black reaction mixture
  8. filtrationwas filtered through a pad of Celite
  9. filtrationfilter (Teflon)
  10. concentrationThe filtrate was concentrated to an amber oil
  11. additionThe oil was diluted
  12. customwith degassed double
  13. filtrationthe mixture filtered (Millipore, Metricel)

Sources & evidence

ORD record
ord-f497dfe4329048c7a549173a132c27ca
Source dataset
uspto-grants-1987_01
Patent number
US04636560

Reaction notes

Loading…