Trifluoroacetic acid → HCID 66861414, compound

HRID 253534Notes

Reaction equation

HRID 253534 reaction equation
C(O)(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(N(CC)CC)C.Cl[C:42]([O:44][CH3:45])=[O:43]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:45][O:44][C:42]([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:43]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 59382869HCID 59382869, compound

Product 1

HCID 66861414HCID 66861414, compoundYield 69.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a 100 mL round bottom flask were added the TFA salt of (R)-tert-butyl 3-((S)-4-amino-1-(3-chlorophenyl)-1-hydroxybutyl)piperidine-1-carboxylate (0.8164 g, 1.64 mmol, 1.0 equiv), DMAP (0.542 g), CH2Cl2 (40 mL) and triethylamine (6 mL). The mixture was cooled in an ice bath and a solution of methyl chloroformate (0.550 g, 5.82 mmol, 3.5 equiv) in CH2Cl2 (10 mL) was added. The reaction mixture was allowed to slowly warm to rt and stirred overnight. 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, 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 0.5020 g (69%) of (R)-tert-butyl 3-((S)-4-(methoxycarbonyl-amino)-1′-(3-chlorophenyl)1-hydroxybutyl)piperidine-1-carboxylate. LC-MS (3 min) tR=1.91 min, m/z 463 (MNa+), 441 (MH+), 343 341; 1H NMR (400 MHz, CDCl3) δ 7.37-7.36 (m, 1H), 7.28-7.17 (m, 3H), 4.90 (br s, 2H), 4.37 (d, J=12.0 Hz, 1H), 3.97 (d, J=12.3 Hz, 1H), 3.64 (s, 3H), 3.16-3.04 (m, 2H), 2.58-2.49 (m, 2H), 1.98-1.86 (m, 2H), 1.76-1.70 (m, 1H), 1.61-1.56 (m, 1H), 1.45 (s, 9H), 1.48-1.13 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 157.60, 155.31, 146.51, 134.31, 129.36, 126.72, 125.96, 123.76, 80.08, 77.65, 52.21, 46.45, 44.91, 44.56, 40.91, 35.97, 28.42, 25.33, 25.25, 24.34.

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) 100 A, 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-4c208ed6557f471a91b56b4aef947846
Source dataset
uspto-grants-2011_01
Patent number
US07872028B2

Reaction notes

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