Potassium tert-butoxide → Tert-butyl 5-chloro-4-((2-cyanoadamantan-2-yl)methoxy)-2-fluorobenzoate

HRID 1849771Notes

Reaction equation

HRID 1849771 reaction equation
[OH:1][CH2:2][C:3]1([C:13]#[N:14])[CH:10]2[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:12][CH:4]1[CH2:5]3)[CH2:9]2.[C:15]([O:19][C:20](=[O:30])[C:21]1[CH:26]=[C:25]([Cl:27])[C:24](F)=[CH:23][C:22]=1[F:29])([CH3:18])([CH3:17])[CH3:16].CC(C)([O-])C.[K+]>CS(C)=O.C(OCC)(=O)C>[Cl:27][C:25]1[C:24]([O:1][CH2:2][C:3]2([C:13]#[N:14])[CH:4]3[CH2:12][CH:8]4[CH2:7][CH:6]([CH2:11][CH:10]2[CH2:9]4)[CH2:5]3)=[CH:23][C:22]([F:29])=[C:21]([CH:26]=1)[C:20]([O:19][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:30]

Participants

6

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 58042499tert-butyl 5-chloro-2,4-difluorobenzoateHCID 867036522-(Hydroxymethyl)adamantane-2-carbonitrile

Product 1

HCID 86703653Tert-butyl 5-chloro-4-((2-cyanoadamantan-2-yl)methoxy)-2-fluorobenzoateYield 79%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(hydroxymethyl)adamantane-2-carbonitrile (0.369 g, 1.93 mmol) and tert-butyl-5-chloro-2,4-difluorobenzoate (0.96 g, 3.86 mmol) in dimethylsulfoxide (30 mL) was added potassium tert-butoxide (0.42 g, 3.76 mmol). The mixture was stirred at ambient temperature for 0.5 hour, then diluted with ethyl acetate (200 mL). The organic layer was washed with 1 M hydrochloric acid (200 mL), brine (2×150 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by column chromatography with a gradient of 0-30% ethyl acetate in hexanes to afford the title compound (0.64 g, 79% yield) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 7.88 (d, J=7.6 Hz, 1H), 6.65 (d, J=11.7 Hz, 1H), 4.29 (s, 2H), 2.36-2.30 (m, 4H), 2.02 (br s, 1H), 1.91-1.74 (m, 9H), 1.56 (s, 9H); MS (ES−) m/z 420.1 (M+1).

Workup

  1. washThe organic layer was washed with 1 M hydrochloric acid (200 mL), brine (2×150 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo to dryness
  5. customThe residue was purified by column chromatography with a gradient of 0-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-7c52405ddf7549688afb3f5f76c90aa0
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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