Trifluoroacetic acid → HCID 59383032, compound

HRID 2266198Notes

Reaction equation

HRID 2266198 reaction equation
[C:1](O)([C:3](F)(F)F)=[O:2].[NH2:8][CH2:9][CH2:10][CH2:11][C@:12]([C@@H:21]1[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22]1)([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=1)[OH:13].C(N(CC)CC)C.C(OC(=O)C)(=O)C>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([NH:8][CH2:9][CH2:10][CH2:11][C@:12]([C@@H:21]1[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22]1)([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=1)[OH:13])(=[O:2])[CH3:3]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 59382869HCID 59382869, compound

Product 1

HCID 59383032HCID 59383032, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a 100 mL, round bottom flask were added TFA salt of (R)-tert-butyl 3-((S)-4-amino-1-(3-chlorophenyl)-1-hydroxybutyl)piperidine-1-carboxylate (0.374 g, 0.75 mmol, 1.0 equiv), DMAP (0.1615 g), CH2Cl2 (10 mL), and triethylamine (3 mL). The mixture was cooled in an ice bath and a solution of acetic anhydride (0.280 g, 2.74 mmol, 3.6 equiv) in CH2Cl2 (10 mL) was added. The reaction mixture was allowed to slowly warm to rt while stirring overnight (16 h). After the solvents were removed in vacuo, the residue was purified by reversed-phase HPLC (Phenomenex® Luna 5μ C18(2) 100A, 250×21.20 mm, 5 micron, 70%→90% CH3CN/H2O, 0.1% CF3COOH over 8 min and then 90% CH3CN/H2O, 0.1% CF3COOH over 1.5 min, flow rate 25 mL/min) to give 0.2589 g (81%) of (R)-tert-butyl 3-((S)-4-acetamido-1-(3-chlorophenyl)-1-hydroxybutyl)-piperidine-1-carboxylate. LC-MS (3 min) tR=1.72 min, m/z 447, 449 (MNa+), 425 (MH+), 325, 327; 1H NMR (400 MHz, CDCl3) □ 7.38-7.37 (m, 1H), 7.28-7.18 (m, 3H), 6.06 (br s, 1H), 4.36-4.34 (m, 1H), 3.97-3.95 (m, 1H), 3.35-3.26 (m, 1H), 3.13-3.05 (m, 1H), 2.99 (br s, 2H), 2.55-2.49 (m, 2H), 1.97 (s, 3H), 1.44 (s, 9H), 1.95-1.15 (m, 6H); 13C NMR (100 MHz, CDCl3) □ 171.41, 155.17, 146.75, 134.24, 129.33, 126.63, 126.01, 123.83, 79.68, 77.60, 46.34, 44.69, 39.71, 35.91, 28.43, 25.40, 25.23, 24.15, 22.99.

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. customAfter the solvents were removed in vacuo
  3. customthe residue was purified by reversed-phase HPLC (Phenomenex® Luna 5μ C18(2) 100A, 250×21.20 mm, 5 micron, 70%
  4. customover 8 min
  5. wait90% CH3CN/H2O, 0.1% CF3COOH over 1.5 min

Sources & evidence

ORD record
ord-11ed6832828c4a95916bf51998a8e98c
Source dataset
uspto-grants-2010_12
Patent number
US07858624B2

Reaction notes

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