Hydrogen Bromide → [3-(Bromomethyl)-1-tosylazetidin-3-yl]methanol

HRID 874725Notes

Reaction equation

[C:1]1([CH3:17])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[CH2:16][C:12]3([CH2:15][O:14][CH2:13]3)[CH2:11]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[BrH:18].C([O-])(O)=O.[Na+]>CCOCC>[Br:18][CH2:13][C:12]1([CH2:15][OH:14])[CH2:16][N:10]([S:7]([C:4]2[CH:5]=[CH:6][C:1]([CH3:17])=[CH:2][CH:3]=2)(=[O:9])=[O:8])[CH2:11]1

Participants

Conditions

Temperature: 0 °C

Procedure

6-(p-Toluenesulfonyl)-2-oxa-6-azaspiro[3.3]heptane (7.99 g, 31.5 mmol) was suspended in Et2O (300 mL) and cooled to 0° C. A solution of HBr (48% in AcOH; 10 mL) in Et2O (20 mL) was added dropwise over 20 min. The resulting mixture was warmed to rt and stirred for 1 h. Reaction was monitored by LC-MS. NaHCO3 (aq. satd., 200 mL) was added and the resulting phases were separated. The aq layer was extracted with Et2O (100 mL) and then combined Et2O layer was dried (MgSO4), filtered, concentrated to dryness to give the title compound as a white solid (10.2 g, 97%). 1H NMR (400 MHz, CDCl3) δ ppm 7.74 (d, J=8.3 Hz, 2H), 7.40 (d, J=8.0 Hz, 2H), 3.69 (d, J=4.8 Hz, 2H), 3.62 (d, J=8.5 Hz, 2H), 3.55 (d, J=8.5 Hz, 2H), 3.46 (s, 2H), 2.48 (s, 3H), 1.55 (t, J=5.0 Hz, 1H); MS ESI 333.9, 335.9 [M+H]+, calcd for [C12H16BrNO3S+H]+334.0, 336.0.

Workup

temperatureThe resulting mixture was warmed to rt
customReaction
customthe resulting phases were separated
extractionThe aq layer was extracted with Et2O (100 mL)
dry with materialcombined Et2O layer was dried (MgSO4)
filtrationfiltered
concentrationconcentrated to dryness

Sources & evidence

ORD record: ord-2b6f645e21f942dbb8e9180bf218e0bd
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08980934B2

Reaction notes

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