Trifluoroacetic acid → HCID 10184630, compound

HRID 2422336Notes

Reaction equation

HRID 2422336 reaction equation
FC(F)(F)C(O)=O.C([O:12][C:13](=[O:45])[CH2:14][CH:15]([NH:20][C:21]([CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][N:24]1[C:29]([N:31]1[C:44]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[S:38][C:37]2[C:32]1=[CH:33][CH:34]=[CH:35][CH:36]=2)=[O:30])=[O:22])[C:16](=[O:19])[CH2:17][F:18])(C)(C)C>C(Cl)Cl>[F:18][CH2:17][C:16](=[O:19])[CH:15]([NH:20][C:21]([CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][N:24]1[C:29]([N:31]1[C:44]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[S:38][C:37]2[C:32]1=[CH:33][CH:34]=[CH:35][CH:36]=2)=[O:30])=[O:22])[CH2:14][C:13]([OH:45])=[O:12]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86585180HCID 86585180, compound

Product 1

HCID 10184630HCID 10184630, compoundYield 66.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Trifluoroacetic acid (5 mL) was added to a stirred ice cold solution of [3S/R, (2S)]-5-fluoro-4-oxo-3-{[1-(phenothiazine-10-carbonyl)piperidine-2-carbonyl]amino}-pentanoic acid tert-butyl ester (130 mg, 0.24 mmol) in anhydrous DCM (5 mL). The mixture was stirred at 0° C. for 0.5 h then at room temperature for 0.5 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 gum was lyophilized twice from HPLC grade water to afford the title compound as a white powder (77 mg, 66%): IR (solid) 1670, 1716, 1782 cm−1; 1H NMR (400 MHz, d6-DMSO) δ 0.96-0.99 (1H, m), 1.23-1.26 (2H, m), 1.42-1.44 (1H, m), 1.60 (1H, m), 1.91-1.98 (1H, m), 2.51-2.89 (2H, m), 3.11-3.22 (1H, m), 3.57-3.60 (1H, m), 4.30-4.72 and 5.05-5.29 (4H, 2 m), 7.11-7.17 (2H, m), 7.24-7.30 (2H, m), 7.34-7.38 (2H, m), 7.57-7.63 (2H, m), 8.07-8.61 (1H, m); 13C NMR (100 MHz, DMSO) δ (DMSO+TFA) 18.8/18.9 (CH2), 22.2/22.3 (CH2), 25.8/26.1 (CH2), 31.5/33.2 (CH2) 43.2 (CH2), 50.6/51.1 (CH), 54.4/54.5 (CH), 82.8/82.9 (2d, J 178.6/178.1, CH2F), 119.9/120.0 (CH), 120.4/120.5 (CH), 124.0/124.1 m (CH), 125.9/126.0 (C), 126.4/126.5 (CH), 139.6/139.7 (C), 156.0/156.4 (CO), 170.3 (CO), 170.7/170.8 (CO), 202.2/202.3 (2d, J 14.6/15.1, CO).; 19F (376 MHz, DMSO) δ chemical shift (multiplicity, relative intensity) −226.7 (t, 3), −226.9 (t, 3), −230.4 (t, 1), −231.2 (t, 1), −232.7 (t, 10), −233.0 (t, 10).

Workup

  1. waitat room temperature for 0.5 h
  2. concentrationThe mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in dry DCM
  4. customto remove excess trifluoroacetic acid

Sources & evidence

ORD record
ord-6acfe852d52347e0a42415e805f5e652
Source dataset
uspto-grants-2011_06
Patent number
US07960398B2

Reaction notes

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