Triphenylphosphine → 3-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)-6-chloropyridine

HRID 367063Notes

Reaction equation

HRID 367063 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][OH:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:14][C:15]1[CH:20]=[CH:19][C:18](O)=[CH:17][N:16]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:18]1[CH:17]=[N:16][C:15]([Cl:14])=[CH:20][CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 8198212-Chloro-5-hydroxypyridineHCID 5462977Diethyl azodicarboxylateHCID 10511797tert-butyl (2S)-2-(hydroxymethyl)azetidine-1-carboxylate

Product 1

HCID 105182243-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)-6-chloropyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 950 mg (5.1 mmol) sample of 1-t-butyloxycarbonyl-2-(S)-azetidinemethanol, prepared as in Example 7c above, and 550 mg (4.25 mmol) of 2-chloro-5-hydroxypyridine (Example 1g above) were added to a solution of triphenylphosphine and DEAD (5.1 mmol each) in 20 mL of THF, according to the procedure of Example 12a, to give 1.09 g of 3-(1-t-butyloxycarbonyl-(2S)-azetidinylmethoxy)-6-chloropyridine: [α]D25 -67.3 (c 1.1, CHCl3); 1H NMR (DMSO-d6, 300 MHz) δ 8.14 (d, J=3.3 Hz, 1H), 7.48 (dd, J=8.8, 3.3 Hz, 1H), 7.37 (d, J=8.8 Hz, 1H), 4.47-4.42 (m, 1H), 4.36 (dd, J=11.0, 4.4 Hz, 1H), 4.20 (dd, J=11.0, 3.3 Hz, 1H), 3.77 (t, J=7.7 Hz, 2H), 2.36-2.29 (m, 1H), 2.19-2.12 (m, 1H), 1.36 (s, 9H); MS (CI/NH3) m/z: 299/301 (M+H)+. A portion of this material (1.02 g) was stirred with 10 mL of 4.5 N HCl at room temperature for 30 minutes. The solvent was removed, and the residue was recrystallized from methanol/ether, to afford 340 mg of the title compound: mp 113-115° C.; 1H NMR (D2O, 300 MHz) δ: 8.15 (d, J=3.0 Hz, 1H), 7.57 (dd, J=8.9, 3.0 Hz, 1H), 7.47 (d, J=8.9 Hz, 1H), 4.98-4.89 (m, 1H), 4.42 (d, J=4.4 Hz, 2H), 4.19-4.02 (m, 2H), 2.68 (q, J=8.5 Hz, 2H); MS (CI/NH3) m/z: 299/301 (M+H)+. Anal. Calcd for C9H13N2OCl3 : C, 39.80; H, 4.82; N, 10.32; Found C, 40.12 H, 4.84; N, 10.35.

Sources & evidence

ORD record
ord-5368c60bab6546d584600d3675825ac5
Source dataset
uspto-grants-2000_10
Patent number
US06133253

Reaction notes

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