Triethylamine → Tert-butyl 3-bromo-5-(5-oxa-6-azaspiro[3.4]oct-6-en-7-yl)benzoate

HRID 1257529Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13](/[CH:15]=[N:16]/[OH:17])[CH:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].ClN1C(=O)CCC1=O.[CH2:26]=[C:27]1[CH2:30][CH2:29][CH2:28]1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CN(C)C=O>[Br:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([C:15]2[CH2:26][C:27]3([CH2:30][CH2:29][CH2:28]3)[O:17][N:16]=2)[CH:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of tert-butyl 3-bromo-5-[(E)-(hydroxyimino)methyl]benzoate (5.26 g, 17.5 mmol) in N,N-dimethylformamide (80 mL)) was added N-chlorosuccinimide (2.57 g, 19.3 mmol). The reaction mixture was heated to 50° C. After 1 h, the reaction was cooled to ambient temperature and methylenecyclobutane (6.49 mL, 70.1 mmol) was added. Triethylamine (12.2 mL, 88.0 mol) was added. The mixture was stirred at ambient temperature. After 10 min, saturated aqueous NaHCO3 was added and the mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with water (2×), brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→90% hexanes/ethyl acetate) gave the title compound (2.86 g). MS 366 (M).

Workup

temperaturethe reaction was cooled to ambient temperature
waitAfter 10 min
extractionthe mixture was extracted with ethyl acetate (3×)
washThe combined organic extracts were washed with water (2×), brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customPurification by silica gel chromatography (100% hexanes→90% hexanes/ethyl acetate)

Sources & evidence

ORD record: ord-2748f007a4b2492e92b261c7007d960b
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461185B2

Reaction notes

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