Trifluoroacetic acid → HCID 59201442, compound

HRID 451712Notes

Reaction equation

HRID 451712 reaction equation
C(O)(C(F)(F)F)=O.[NH2:8][CH2:9][CH2:10][CH2:11][CH:12]([C@@H:20]1[CH2:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]1)[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1.CCN(C(C)C)C(C)C.Cl[C:43]([O:45][CH3:46])=[O:44]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[F:19][C:15]1[CH:14]=[C:13]([CH:12]([C@@H:20]2[CH2:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]2)[CH2:11][CH2:10][CH2:9][NH:8][C:43]([O:45][CH3:46])=[O:44])[CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 59201457HCID 59201457, compound

Product 1

HCID 59201442HCID 59201442, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A 100 mL round bottom flask was charged with 0.092 g of TFA salt of (3S)-tert-butyl 3-(4-amino-1-(3-fluorophenyl)butyl)piperidine-1-carboxylate, 0.152 g of DMAP, 10 mL of CH2Cl2, and 2 mL of DIPEA. The mixture was cooled with an ice bath and then a solution of methyl chloroformate (0.280 g) in CH2Cl2 (3 mL) was added. The reaction mixture was allowed to slowly warm to rt while stirring overnight. After the reaction mixture was evaporated under reduced pressure, the crude product was purified by reversed-phase 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 2 min, flow rate 25 mL/min) to afford 0.0306 g (38%) of (3S)-tert-butyl 3-(1-(3-fluorophenyl)-4-(methoxycarbonylamino)butyl)piperidine-1-carboxylate. Isomer 1 and 2, MS ESI +ve m/z 431 (MNa+), 409 (MH+), tR=1.91, 1.98 min in 3 min chromatography.

Workup

  1. temperatureThe mixture was cooled with an ice bath
  2. customAfter the reaction mixture was evaporated under reduced pressure
  3. customthe crude product was purified by reversed-phase HPLC (Phenomenex® Luna 5μ C18(2) 100 A, 250×21.20 mm, 5 micron, 70%
  4. customover 8 min
  5. wait90% CH3CN/H2O, 0.1% CF3COOH over 2 min

Sources & evidence

ORD record
ord-f4af3422d72d4ff4ad4f4d60fb5b7336
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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