Trifluoroacetic acid → Trifluoroacetic acid

HRID 451891Notes

Reaction equation

HRID 451891 reaction equation
[C:1](=[O:44])([O:3][CH2:4][CH2:5][O:6][C@@H:7]([C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[CH:38]=1)[C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:36])[NH:15][C@H:16]([CH2:24][NH:25][CH2:26]C(OCC[Si](C)(C)C)=O)[CH2:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:9]1)[NH2:2].[F:45][C:46]([F:51])([F:50])[C:47]([OH:49])=[O:48]>C(Cl)Cl>[C:1](=[O:44])([O:3][CH2:4][CH2:5][O:6][C@@H:7]([C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[CH:38]=1)[C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:36])[NH:15][C@H:16]([CH2:24][NH:25][CH3:26])[CH2:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:9]1)[NH2:2].[C:47]([OH:49])([C:46]([F:51])([F:50])[F:45])=[O:48]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68716498HCID 68716498, compound

Product 2

HCID 6422Trifluoroacetic acidYield 86%HCID 59201427HCID 59201427, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-cyclohexyl-3-(2-(trimethylsilyl)ethoxycarbonylmethylamino)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethyl carbamate (0.0250 g, 0.038 mmol) and trifluoroacetic acid (1 mL) in CH2Cl2 (5 mL) was stirred at rt for 3 h. After the solvents were removed in vacuo, the residue was purified by reversed-phase HPLC (Phenomenex® Luna 5μ C18(2) 100 A, 250×21.20 mm, 5 micron, 10%→90% CH3CN/H2O, 0.1% CF3COOH over 13 min, flow rate 25 mL/min) to give 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-cyclohexyl-3-(methylamino)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethyl carbamate as its TFA salt (0.0205 g, 86%). LC-MS (3 min) tR=1.49 min, m/z 511, 509 (MH+); 1H NMR (400 MHz, CD3OD) δ 7.28-7.12 (m, 4H), 4.20 (d, J=13.2 Hz, 1H), 4.11-3.99 (m, 3H), 3.95 (d, J=8.8 Hz, 1H), 3.87 (d, J=13.2 Hz, 1H), 3.40-3.28 (m, 2H), 2.96 (dd, J=12.6, 3.2 Hz, 1H), 2.84 (dd, J=12.6, 10.2 Hz, 1H), 2.73-2.63 (m, 2H), 2.61 (s, 3H), 1.71-0.75 (m, 18H).

Workup

  1. customAfter the solvents were removed in vacuo
  2. customthe residue was purified by reversed-phase HPLC (Phenomenex® Luna 5μ C18(2) 100 A, 250×21.20 mm, 5 micron, 10%→90% CH3CN/H2O, 0.1% CF3COOH over 13 min, flow rate 25 mL/min)

Sources & evidence

ORD record
ord-24c4d11c37b445948ae42bc33109579a
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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