Tert-butyl 3-hydroxyazetidine-1-carboxylate → Tert-butyl 3-(2-methoxy-4-nitrophenoxy)azetidine-1-carboxylate

HRID 2384893Notes

Reaction equation

F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[O:11][CH3:12].[C:13]([O:17][C:18]([N:20]1[CH2:23][CH:22]([OH:24])[CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(O[K])(C)(C)C>C1COCC1.O>[C:13]([O:17][C:18]([N:20]1[CH2:23][CH:22]([O:24][C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=2[O:11][CH3:12])[CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

Conditions

Temperature: 0 °C

Procedure

Dissolve 1-fluoro-2-methoxy-4-nitro-benzene (118 g, 689 mmol) and 3-hydroxy-azetidine-1-carboxylic acid tert-butyl ester (125 g, 724 mmol) in THF (800 mL) and cool to 0° C. To the above solution under a nitrogen atmosphere, add dropwise a 1M solution of tBuOK (1 L, solution in THF). After addition is complete, stir the dark brown solution for 30 min at 0° C., then dilute with water (1 L) over a 10 min period. Stir the mixture for 5 min, then extract with MTBE twice. Combine the organic solutions and wash with brine (2×700 mL), then dry and concentrate. Dry the solid in vacuo at 45° C. for 20 h to obtain 216 g (95%) of the title compounds as a yellow solid. 1H NMR (300 MHz, CDCl3) δ1.42 (s, 9H), 3.80 (s, 3H), 4.04 (m, 2H), 4.18 (m, 2H), 4.76 (m, 1H), 6.17 (dd, 1H, J=2.4, 8.5), 6.30 (d, 1H, J=2.6), 6.47 (d, 1H, J=8.5).

Workup

additionAfter addition
stirringStir the mixture for 5 min
extractionextract with MTBE twice
washwash with brine (2×700 mL)
customdry
concentrationconcentrate
customDry the solid in vacuo at 45° C. for 20 h

Sources & evidence

ORD record: ord-b86a8cca4b934209a4e51d6bf29810d3
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08263772B2

Reaction notes

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