Cesium carbonate → Tert-butyl 2-[4-[4-(trifluoromethylsulfonyl)anilino]cyclohexoxy]acetate

HRID 1772290Notes

Reaction equation

HRID 1772290 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][CH:5]([O:8][CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:4][CH2:3]1.Br[C:18]1[CH:23]=[CH:22][C:21]([S:24]([C:27]([F:30])([F:29])[F:28])(=[O:26])=[O:25])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[F:29][C:27]([F:28])([F:30])[S:24]([C:21]1[CH:22]=[CH:23][C:18]([NH:1][CH:2]2[CH2:7][CH2:6][CH:5]([O:8][CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:4][CH2:3]2)=[CH:19][CH:20]=1)(=[O:25])=[O:26]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 3001141-Bromo-4-trifluoromethanesulfonylbenzeneHCID 10680931Tert-butyl 2-(4-aminocyclohexoxy)acetate

Product 1

HCID 86719526Tert-butyl 2-[4-[4-(trifluoromethylsulfonyl)anilino]cyclohexoxy]acetateYield 98.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of tert-butyl 2-(4-aminocyclohexoxy)acetate (0.5 g, 1.7 mmol, 1 eq.), 1-bromo-4-(trifluoromethylsulfonyl)benzene (0.4 g, 1.7 mmol, 1 eq.), cesium carbonate (1.4 g, 4.3 mmol, 2.5 eq.), and BINAP (54 mg, 0.08 mmol, 0.05 eq.), in toluene (15 mL), was bubbled with nitrogen for 10 minutes before the addition of Pd(OAc)2 (19 mg, 0.08 mmol, 0.05 eq.) to the reaction mixture. Nitrogen gas was bubbled through the reaction mixture for another 10 minutes and the contents were heated at 100° C. under nitrogen atmosphere for 3 hours. The contents were cooled to room temperature, diluted with ethyl acetate, filtered through Celite®, and concentrated. The crude material was purified by silica gel column chromatography using ethyl acetate/heptanes to elute. The product containing fractions were combined and concentrated to obtain tert-butyl 2-[4-[4-(trifluoromethylsulfonyl)anilino]cyclohexoxy]acetate (0.73 g, 77%); (CI, m/z): [M+H]+ 438; 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J=8.9 Hz, 2H), 6.56-6.70 (m, 2H), 4.44 (d, J=7.4 Hz, 1H), 4.02 (s, 2H), 3.32-3.49 (m, 2H), 2.07-2.25 (m, 4H), 1.44-1.55 (m, 11H), 1.21-1.35 (m, 2H).

Workup

  1. customNitrogen gas was bubbled through the reaction mixture for another 10 minutes
  2. temperatureThe contents were cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. filtrationfiltered through Celite®
  5. concentrationconcentrated
  6. customThe crude material was purified by silica gel column chromatography
  7. washto elute
  8. additionThe product containing fractions
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-20714f17df9d4fc2a4b2a7d3457beb87
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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