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

HRID 633908Notes

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-af5000ac5e6741b8afe6f573ab92f27e
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321769B2

Reaction notes

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