Triphenylphosphine → Methyl 6-((1-(tert-butoxycarbonyl)pyrrolidin-2-yl)methoxy)-5-chloronicotinate

HRID 354325Notes

Reaction equation

[Cl:1][C:2]1[C:3]([OH:12])=[N:4][CH:5]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:7]=1.[C:13]([O:17][C:18]([N:20]1[CH2:26][CH2:25][CH2:24][C@H:21]1[CH2:22]O)=[O:19])([CH3:16])([CH3:15])[CH3:14].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Cl:1][C:2]1[C:3]([O:12][CH2:22][CH:21]2[CH2:24][CH2:25][CH2:26][N:20]2[C:18]([O:17][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:19])=[N:4][CH:5]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:7]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a stirred solution of methyl 3-chloro-2-hydroxypyridine-5-carboxylate (300 mg, 1.599 mmol), N-tert-butoxycarbonylprolinol (321.9 mg, 1.599 mmol), and Ph3P (503 mg, 1.919 mmol) in THF (3 mL) was slowly added DIAD (378 μl, 1.919 mmol) at room temp, and the mixture was stirred for 13 hr at 70° C. The mixture was concentrated and the residue was chromatographed on silica-gel with n-hexane-EtOAc (3:1, v/v) as eluent to give 235.6 mg (40%) methyl 3-chloro-2-[[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy]pyridine-5-carboxylate as a pale yellowish oil. 1H-NMR (400 MHz, CDCl3) δ1.46 (s, 9H), 1.87 (m, 1H), 2.05 (br s, 3H), 3.43 (br s, 2H), 3.92 (s, 3H), 4.17, 4.26 (br s each, 1H), 4.45-4.51 (m, 1H), 4.50 (s, 1H), 8.21 (s, 1H), (s, 1H), 8.67 (d, J=2.0 Hz, 1H); MS (FAB) m/z 371 (M++1).

Workup

customat room temp
concentrationThe mixture was concentrated
customthe residue was chromatographed on silica-gel with n-hexane-EtOAc (3:1

Sources & evidence

ORD record: ord-ba3bf7bf7b6f4ad3976474d0eefce6af
Source dataset: uspto-grants-2004_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06756378B2

Reaction notes

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