Tert-butyl 2-(acetoxymethyl)-4-oxopiperidine-1-carboxylate → tert-butyl 3-(acetoxymethyl)-8-bromo-6-chloro-1,4,4a,9b-tetrahydrobenzofuro[3,2-c]pyridine-2(3H)-carboxylate

HRID 2179414Notes

Reaction equation

HRID 2179414 reaction equation
[C:1]([O:4][CH2:5][CH:6]1[CH2:11][C:10](=[O:12])[CH2:9][CH2:8][N:7]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])(=[O:3])[CH3:2].Cl.[Br:21][C:22]1[CH:27]=[CH:26][C:25](ON)=[C:24]([Cl:30])[CH:23]=1>>[C:1]([O:4][CH2:5][CH:6]1[N:7]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8][CH:9]2[C:26]3[CH:27]=[C:22]([Br:21])[CH:23]=[C:24]([Cl:30])[C:25]=3[O:12][CH:10]2[CH2:11]1)(=[O:3])[CH3:2]

Participants

3

Reactant 2

HCID 68109076Tert-butyl 2-(acetoxymethyl)-4-oxopiperidine-1-carboxylateHCID 68109187O-(2-chloro-4-bromophenyl)hydroxylamine hydrochloride

Product 1

HCID 68108210tert-butyl 3-(acetoxymethyl)-8-bromo-6-chloro-1,4,4a,9b-tetrahydrobenzofuro[3,2-c]pyridine-2(3H)-carboxylateYield 8%

Procedure

The product obtained from step I (1.33 g, 4.9 mmol) was reacted with O-(4-bromo-2-chlorophenyl)hydroxylamine hydrochloride following the procedure of Example 29 step B. Purification by column chromatography (SiO2, 49:1 to 19:1 hexanes/ethyl acetate) afforded tert-butyl 3-(acetoxymethyl)-8-bromo-6-chloro-1,4,4a,9b-tetrahydrobenzofuro[3,2-c]pyridine-2(3H)-carboxylate (203 mg, 8%) as a colorless oil: 1H NMR (CDCl3, 300 MHz) δ 7.43 (s, 1H), 7.38 (d, J=1.8 Hz, 1H), 5.14 (br s, 2H), 4.10-4.07 (m, 3H), 3.16-3.14 (m, 1H), 2.80 (d, J=17.4 Hz, 1H), 2.04 (s, 3H), 1.52 (s, 9H).

Workup

  1. customPurification by column chromatography (SiO2, 49:1 to 19:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-58b6195ca77541428c31b6e63bbcb982
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

Loading…