Sodium hydride → Tert-butyl 3-(1,3-thiazol-2-ylmethoxy)azetidine-1-carboxylate

HRID 82952Notes

Reaction equation

[C:1]([N:8]1[CH2:11][CH:10]([OH:12])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].[Cl-].Cl[CH2:17][C:18]1[S:19][CH:20]=[CH:21][NH+:22]=1>CN(C=O)C.CCN(C(C)C)C(C)C.O>[S:19]1[CH:20]=[CH:21][N:22]=[C:18]1[CH2:17][O:12][CH:10]1[CH2:11][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of N-Boc-azetidin-3-ol (260 mg, 1.5 mmol) in DMF (3.5 mL) at 0° C. under nitrogen was added NaH (60% in oil, 126 mg, 3.15 mmol). The suspension was stirred for 0.5 h at 0° C. then treated with 2-(chloromethyl)-1,3-thiazol-3-ium chloride (510 mg, 3.0 mmol; which may be prepared as described in Step 1) dissolved in DMF (1 mL) and DIPEA (1.05 mL). The mixture was allowed to warm to room temperature then heated to 80° C. overnight. The reaction mixture was cooled, water (20 drops) was added and the mixture concentrated under reduced pressure. The crude material was purified on column chromatography (eluent: Pentane/EtOAc, 90/10 to 50/50) to give the product (193 mg, 48%) as a brown oil.

Workup

temperatureto warm to room temperature
temperaturethen heated to 80° C. overnight
temperatureThe reaction mixture was cooled
concentrationthe mixture concentrated under reduced pressure
customThe crude material was purified on column chromatography (eluent: Pentane/EtOAc, 90/10 to 50/50)

Sources & evidence

ORD record: ord-7a0d70ddefcc4ea195d5546260264ea3
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846711B2

Reaction notes

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