HCID 22961823, compound → HCID 53973969, compound

HRID 367067Notes

Reaction equation

HRID 367067 reaction equation
[Cl:1][C:2]1[C:7]([CH:8]=[CH2:9])=[CH:6][C:5]([O:10][CH2:11][C@@H:12]2[CH2:15][CH2:14][N:13]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:4][N:3]=1>CO.[Pt]>[Cl:1][C:2]1[C:7]([CH2:8][CH3:9])=[CH:6][C:5]([O:10][CH2:11][C@@H:12]2[CH2:15][CH2:14][N:13]2[C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])=[CH:4][N:3]=1

Participants

4

Reactant 1

HCID 22961823HCID 22961823, compound

Product 1

HCID 53973969HCID 53973969, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 887MethanolSolvent

Procedure

A suspension of 5% Pt on carbon and 2-chloro-3-vinyl-5-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)pyridine (Example 26 above, 440 mg, 1.36 mmol) in MeOH (10 mL) were stirred overnight under an atmosphere of hydrogen (balloon). The mixture was filtered and the filtrate was concentrated to afford 2-chloro-3-ethyl-5-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)pyridine as a colorless oil (219 mg, 51%): 1H NMR (CDCl3, 300 MHz) δ 1.25 (t, J=7.5 Hz, 3H), 1.42 (s, 9H), 2.32 (m, 2H), 2.71 (q, J=7.5 Hz, 2H), 3.89 (t, J=7.8 Hz, 2H), 4.12 (dd, J=3.0, 9.8 Hz, 1H), 4.30 (m, 1H), 4.50 (m, 1H), 7.16 (d, J=3.1 Hz, 1H), 7.94 (d, J=3.0 Hz, 1H); MS (CI/NH3) m/z 327 (M+H)+. To a solution of the product from above (216 mg, 0.66 mmol) in CH2Cl2 (2 mL) at 0° C. was added trifluoroacetic acid (1.8 miL). The solution was allowed to warm to room temperature, then adjusted to pH 11 with aqueous 10% NaOH, and extracted with CH2Cl2. The organic extract was dried over MgSO4 and concentrated. The residue was chromatographed (silica gel; CH2Cl2 /MeOH, 100:3 to 100:15) to afford the free base of the title compound as an oil (60 mg, 40%): 1H NMR (CDCl3, 300 MHz) δ 1.22 (m 3H), 2.38 (m, 2H), 2.71 (q, J=7.5 Hz, 2H), 3.57 (m, 1H), 3.80 (m, 1H), 4.08 (m, 2H), 4.38 (m, 1H), 7.15 (d, J=2.4 Hz, 1H), 7.92 (d, J=3.0 Hz, 1H); MS (CI/NH3) m/z: 227 (M+H)+. The free base was dissolved in THF and treated with 1 M HCl in Et2O to afford the hydrochloride salt, which was triturated with Et2O and dried under vacuum to afford the title compound as a white solid: mp 102-104° C.; [α]D23 -9.68 (c 0.62, MeOH); 1H NMR (D2O) δ 1.24 (t, J=7.5 Hz, 3H), 2.71 (m, 4H), 4.11 (m, 2H), 4.42 (d, J=4 Hz, 2H), 4.95 (m, 1H), 7.51 (d, J=3 Hz, 1H), 8.00 (d, J=3 Hz, 1H). Anal. Calcd. for C11H15N2OCl.1.1 HCl: C, 49.52; H, 6.08; N, 10.50. Found: C, 49.63; H, 5.89; N, 10.20.

Workup

  1. filtrationThe mixture was filtered
  2. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-2623c91f9ff744a7a0719106bba9c523
Source dataset
uspto-grants-2000_10
Patent number
US06133253

Reaction notes

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