Tetrahydrofuran → tert-butyl N-[6-chloro-4-(1-hydroxyethyl)-3-pyridyl]carbamate

HRID 468781Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[C:4]([CH:16]=[O:17])[CH:3]=1.O1CCC[CH2:19]1.C[Mg]I>CCOCC>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[C:4]([CH:16]([OH:17])[CH3:19])[CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To an ice-cooled solution of tert-butyl 6-chloro-4-formylpyridin-3-ylcarbamate (1.0091 g, 3.9313 mmol) in tetrahydrofuran (20 mL, 200 mmol) in an oven-dried flask was added 3.0 M of methylmagnesium iodide in ether (3.4 mL). The reaction mixture was stirred at 0° C. for one hour and then quenched with 10 mL saturated aqueous NH4Cl. The resulting mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3, and the organic layer was dried with brine and MgSO4 and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 0-40% ethyl acetate in heptane) to yield 0.870 g (81%) of tert-butyl 6-chloro-4-(1-hydroxyethyl)pyridin-3-ylcarbamate. LCMS (ESI): M+H=273.2; 1H NMR (400 MHz, DMSO) δ 8.89 (s, 1H), 8.43 (s, 1H), 7.45 (s, 1H), 5.76 (s, 1H), 4.95 (d, J=6.4 Hz, 1H), 1.46 (s, 9H), 1.28 (d, J=6.5 Hz, 3H).

Workup

customquenched with 10 mL saturated aqueous NH4Cl
customThe resulting mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3
dry with materialthe organic layer was dried with brine and MgSO4
customevaporated in vacuo
customThe crude product was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 0-40% ethyl acetate in heptane)

Sources & evidence

ORD record: ord-922adc7ef3704102967e09e7670c9176
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623889B2

Reaction notes

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