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

HRID 2172008Notes

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-778c66f41c274567b59cd3d059c4b9b2
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09051321B2

Reaction notes

Loading…