Triethylamine → tert-Butyl (S)-2-(((methylsulfonyl)oxy)methyl)azetidine-1-carboxylate

HRID 10391Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][OH:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:21][S:22](Cl)(=[O:24])=[O:23].C(=O)(O)[O-].[Na+]>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][S:22]([CH3:21])(=[O:24])=[O:23])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

2-(S)-Hydroxymethyl-azetidine-1-carboxylic acid tert-butyl ester (prepared as described in Abreo, et al. J. Med. Chem. 1996, 39, 817–825) (9.7 g, 52 mmol) was taken up in dichloromethane (50 mL), treated with triethylamine (8.7 mL, 62 mmol), cooled to 0° C., treated dropwise with methanesulfonyl chloride (4.4 mL, 57 mmol), stirred overnight at ambient temperature, treated with sodium bicarbonate solution (50 mL) and the layers were separated. The aqueous layer was extracted with dichloromethane (50 mL). The combined organic layers were dried (MgSO4), filtered, concentrated and chromatographed on silica gel eluting with a gradient of 10:1, 5:1, 2:1 and 3:2 hexane:ethyl acetate to provide 10.7 g (78%). 1H NMR (300 MHz, CDCl3) δ 1.45 (s, 9 H) 2.27 (m, 2 H) 3.05 (s, 3 H) 3.82 (m, 2 H) 4.28 (dd, J=10.85, 2.71 Hz, 1 H) 4.43 (m, 1 H) 4.54 (dd, J=10.85, 4.07 Hz, 1 H).

Workup

customthe layers were separated
extractionThe aqueous layer was extracted with dichloromethane (50 mL)
dry with materialThe combined organic layers were dried (MgSO4)
filtrationfiltered
concentrationconcentrated
customchromatographed on silica gel eluting with a gradient of 10:1, 5:1, 2:1 and 3:2 hexane
customethyl acetate to provide 10.7 g (78%)

Sources & evidence

ORD record: ord-e468895d0537455791117c5aa46e01fd
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07094790B2

Reaction notes

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