Trifluoroacetic acid → HCID 67190980, compound

HRID 2355421Notes

Reaction equation

HRID 2355421 reaction equation
[C:1]([OH:7])(C(F)(F)F)=O.[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[CH2:35][N:36](C(C)C)C(C)C.ClC(OC1C=CC([N+]([O-])=O)=CC=1)=O>C1COCC1.C(Cl)Cl>[CH3:35][NH:36][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:7]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 59382869HCID 59382869, compound

Product 1

HCID 67190980HCID 67190980, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of the TFA salt of (R)-tert-butyl 3-((S)-4-amino-1-(3-chlorophenyl)-1-hydroxybutyl)piperidine-1-carboxylate (0.0388 g, 0.078 mmol, 1.0 equiv) in THF (5 mL) and CH2Cl2 (5 mL) at rt were added of DIEA (0.7 mL) and p-nitrophenyl chloroformate (0.0350 g, 0.17 mmol, 2.2 equiv). The mixture was stirred at rt for 3 h. One half of the resulting solution was withdrawn and 33 wt % MeNH2 in EtOH (1.5 mL) was added. The resulting mixture was stirred at rt for 1 h. The solvents were removed in vacuo and the residue was purified by reversed-phase preparative HPLC (Phenomenex® Luna 5μ C18(2) 100 A, 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 7 min, flow rate 25 mL/min) to give (R)-tert-butyl 3-((S)-4-(methylamino-carbonylamino)-1-(3-chlorophenyl)-1-hydroxybutyl)piperidine-1-carboxylate (0.0043 g). LC-MS (3 min) tR=1.71 min, m/z 442, 440 (M+H+), 340.

Workup

  1. customOne half of the resulting solution was withdrawn
  2. addition33 wt % MeNH2 in EtOH (1.5 mL) was added
  3. stirringThe resulting mixture was stirred at rt for 1 h
  4. customThe solvents were removed in vacuo
  5. customthe residue was purified by reversed-phase preparative HPLC (Phenomenex® Luna 5μ C18(2) 100 A, 250×21.20 mm, 5 micron, 70%
  6. customover 8 min
  7. wait90% CH3CN/H2O, 0.1% CF3COOH over 7 min

Sources & evidence

ORD record
ord-beaf09a166e34607b1273514efbcb12e
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

Loading…