Cesium carbonate → HCID 178497927, compound

HRID 906141Notes

Reaction equation

HRID 906141 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[NH2:12][C@H:13]1[CH2:18][CH2:17][C@H:16]([OH:19])[CH2:15][CH2:14]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:19][C@H:16]1[CH2:17][CH2:18][C@H:13]([NH:12][C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=2)[C:5]([O:7][CH3:8])=[O:6])[CH2:14][CH2:15]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 12070Methyl 3-bromobenzoateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 178511715HCID 178511715, compound

Product 1

HCID 178497927HCID 178497927, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of methyl 3-bromobenzoate (0.43 g, 2.00 mmol), trans-4-aminocyclohexanol (0.35 g, 3.00 mmol), cesium carbonate (1.63 g, 5.00 mmol), Xantphos (0.024 g, 0.02 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.010 g, 0.01 mmol) in 1,4-dioxane (25 mL) was stirred at 80° C. under N2 atmosphere for 18 hours. After cooling to room temperature the reaction mixture was filtered through a pad of Celite and was washed with ethyl acetate (200 mL), and the combined filtrate was partitioned with water. The organic layer was separated and washed with 1 M aqueous hydrochloric acid and brine, dried over sodium sulfate, filtered, and the solution was concentrated. The residue was purified by column chromatography (hexane:ethyl acetate 4:1 to 3:2) to give methyl 3-[(trans-4-hydroxycyclohexyl)amino]benzoate. (0.28 g, 56%). 1H NMR (400 MHz, DMSO-d6): 7.18 (m, 2H), 7.08 (m, 1H), 6.82 (m, 1H), 5.82 (d, 1H), 3.84 (s, 3H), 3.34 (m, 1H), 2.57 (m, 1H), 1.85 (m, 2H), 1.71 (m, 2H), 1.58 (m, 2H), 1.46 (m, 2H). MS (EI) for C14H19NO3: 250 (MH+).

Workup

  1. temperatureAfter cooling to room temperature the reaction mixture
  2. filtrationwas filtered through a pad of Celite
  3. washwas washed with ethyl acetate (200 mL)
  4. customthe combined filtrate was partitioned with water
  5. customThe organic layer was separated
  6. washwashed with 1 M aqueous hydrochloric acid and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationthe solution was concentrated
  10. customThe residue was purified by column chromatography (hexane:ethyl acetate 4:1 to 3:2)

Sources & evidence

ORD record
ord-0346c4bf2c064145a9da183506b5aa26
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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