(1-Benzhydrylazetidin-3-yl)methanol → Tert-butyl 4-((1-benzhydrylazetidin-3-yl)methoxy)-5-chloro-2-fluorobenzoate

HRID 1849900Notes

Reaction equation

HRID 1849900 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16]([CH2:18][OH:19])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:20][C:21]1[C:22](F)=[CH:23][C:24]([F:34])=[C:25]([CH:33]=1)[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].CC(C)([O-])C.[K+]>CS(C)=O.CCOC(C)=O>[CH:1]([N:14]1[CH2:17][CH:16]([CH2:18][O:19][C:22]2[C:21]([Cl:20])=[CH:33][C:25]([C:26]([O:28][C:29]([CH3:30])([CH3:31])[CH3:32])=[O:27])=[C:24]([F:34])[CH:23]=2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 2758715(1-Benzhydrylazetidin-3-yl)methanolHCID 23665647Potassium tert-butoxideHCID 58042499tert-butyl 5-chloro-2,4-difluorobenzoate

Product 1

HCID 86703778Tert-butyl 4-((1-benzhydrylazetidin-3-yl)methoxy)-5-chloro-2-fluorobenzoateYield 73%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To solution of (1-benzhydrylazetidin-3-yl)methanol (368 mg) and tert-butyl 5-chloro-2,4-difluoro-benzoate (397 mg) in DMSO (7.3 mL) at 14° C. (bath) was added potassium tert-butoxide (196 mg). The mixture was stirred at rt for 1 hr. Diluted with EtOAc, the contents were washed with 1:4 mixture of 1M HCl and 1M NaH2PO4 (2×) and brine (1×), dried (Na2SO4). After filtration and concentration, the crude was purified with flash chromatography (0-40% EtOAc/heptane) to give the product (511 mg).

Workup

  1. washthe contents were washed with 1:4 mixture of 1M HCl and 1M NaH2PO4 (2×) and brine (1×)
  2. dry with materialdried (Na2SO4)
  3. filtrationAfter filtration and concentration
  4. customthe crude was purified with flash chromatography (0-40% EtOAc/heptane)

Sources & evidence

ORD record
ord-227bc8d337b242088318981b692a5e5d
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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