Water → Tert-butyl 3-(4-formyl-3-methylphenoxy)azetidine-1-carboxylate

HRID 1035234Notes

Reaction equation

[H-].[Na+].[OH:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[C:6]([CH3:12])[CH:5]=1.CS(O[CH:18]1[CH2:21][N:20]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:19]1)(=O)=O.O>CN(C=O)C>[CH:8]([C:7]1[CH:10]=[CH:11][C:4]([O:3][CH:18]2[CH2:19][N:20]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21]2)=[CH:5][C:6]=1[CH3:12])=[O:9]

Participants

Conditions

Temperature: 100 °C

Procedure

A slurry of sodium hydride (60%, 0.12 g, 3.10 mmol) in DMF (4 ml) was cooled by an ice-bath. Under nitrogen, 4-hydroxy-2-methylbenzaldehyde in DMF (2 ml) was added. The mixture was stirred for 30 min and then tert-butyl 3-(methylsulfonyloxy)azetidine-1-carboxylate in DMF (4 ml) was added. The mixture was heated to 100° C. using an oil bath for 3 days and then cooled to RT. Water (100 ml) was added while stirring. The mixture was extracted trice with EtOAc. The combined organic solutions were dried (MgSO4) and then evaporated. The residue was purified by silica gel chromatography eluting with EtOAc/heptane (10:90). There was obtained 120 mg (20%) of partly purified 69A as an oil. 1H NMR (500 MHz, CDCl3): δ 1.46 (s, 9H), 2.64 (s, 3H), 4.01 (m, 2H), 4.33 (m, 2H), 4.94 (m, 1H), 6.60 (d, 1H), 6.66 (dd, 1H), 7.76 (d, 1H), 10.13 (s, 1H).

Workup

customfor 3 days
temperaturecooled to RT
stirringwhile stirring
extractionThe mixture was extracted trice with EtOAc
dry with materialThe combined organic solutions were dried (MgSO4)
customevaporated
customThe residue was purified by silica gel chromatography
washeluting with EtOAc/heptane (10:90)
customThere was obtained 120 mg (20%)
customof partly purified 69A as an oil

Sources & evidence

ORD record: ord-1b01e2bfdec44d3c90a6be033fe70962
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546375B2

Reaction notes

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