Trifluoroacetic acid → 3-[2-(2-Carbazol-9-yl-2-oxo-ethyl)-pentanoylamino]-5-fluoro-4-oxo-pentanoic Acid

HRID 2422346Notes

Reaction equation

HRID 2422346 reaction equation
C1C2N(C(=O)C[C@@H](CCC)C(O)=O)C3C(=CC=CC=3)C=2C=CC=1.C([O:28][C:29](=[O:59])[CH2:30][CH:31]([NH:36][C:37](=[O:58])[CH:38]([CH2:42][C:43]([N:45]1[C:57]2[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=2[C:51]2[C:46]1=[CH:47][CH:48]=[CH:49][CH:50]=2)=[O:44])[CH2:39][CH2:40][CH3:41])[C:32](=[O:35])[CH2:33][F:34])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:56]1[C:57]2[N:45]([C:43](=[O:44])[CH2:42][CH:38]([CH2:39][CH2:40][CH3:41])[C:37]([NH:36][CH:31]([C:32](=[O:35])[CH2:33][F:34])[CH2:30][C:29]([OH:59])=[O:28])=[O:58])[C:46]3[C:51](=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:52]=2[CH:53]=[CH:54][CH:55]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 57418779(2R)-2-(2-carbazol-9-yl-2-oxo-ethyl)-pentanoic acidHCID 723594993-[2-(2-Carbazol-9-yl-2-oxo-ethyl)-pentanoylamino]-5-fluoro-4-oxo-pentanoic acid tert-butyl ester

Product 1

HCID 762172073-[2-(2-Carbazol-9-yl-2-oxo-ethyl)-pentanoylamino]-5-fluoro-4-oxo-pentanoic AcidYield 5.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of [3S/R, (2R)]-3-[2-(2-carbazol-9-yl-2-oxo-ethyl)-pentanoylamino]-5-fluoro-4-oxo-pentanoic acid tert-butyl ester (1.43 g, 2.88 mmol) in anhydrous DCM (20 ml) was treated with a solution of TFA (10 ml) in anhydrous DCM (10 ml) with stirring. The mixture was stirred at 0° C. for 2 h then at room temperature for 2 h. The mixture was concentrated under reduced pressure and then the residue was dissolved in dry DCM. This process was repeated several times in order to remove excess trifluoroacetic acid. The off-white solid was recrystallized from Et2O/40/60 hexanes to give the title compound as a white powder (71 mg): IR (solid, cm−1) 1746, 1689, 1641, 1541, 1436, 1374, 1284, 1207, 1160 cm-1; 1H NMR (400 MHz, d6-DMSO) δ 0.80-1.00 (3H, m), 1.20-1.76 (4H, m), 2.30-2.90 (2H, m), 2.95-3.24 (1H, m), 3.26-3.59 (2H, m), 4.25-4.79 (1.5H, m) 5.02-5.43 (1.5H, m), 7.36-7.58 (4H, m), 8.10-8.30 (4H, m), 8.54-8.91 (1H, m); 13C NMR (100 MHz, DMSO) δ 14.31, 20.03, 20.13, 21.92, 22.51, 34.36, 34.77, 41.20, 41.62, 44.06, 51.77, 52.84, 83.45, 85.22, 116.70, 120.54, 123.91, 124.01, 127.85, 126.01, 138.20, 172.15, 172.36, 172.96, 173.00, 175.32, 175.48, 202.60, 203.10; 19F (376 MHz, DMSO) δ −226.68, −226.73, −231.21, −232.95, −233.38, −233.52.

Workup

  1. stirringThe mixture was stirred at 0° C. for 2 h
  2. concentrationThe mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in dry DCM
  4. customto remove excess trifluoroacetic acid
  5. customThe off-white solid was recrystallized from Et2O/40/60 hexanes

Sources & evidence

ORD record
ord-ce8248ffc375413580bd9cae4af964e9
Source dataset
uspto-grants-2011_06
Patent number
US07960398B2

Reaction notes

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