Cesium carbonate → Tert-butyl 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-4-hydroxycyclohexanecarboxylate

HRID 1039933Notes

Reaction equation

HRID 1039933 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:8]=1)[NH2:5].Br[C:19]1[S:23][C:22]([C:24]2([OH:37])[CH2:29][CH2:28][CH:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)=[N:21][CH:20]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].O.O1CCOCC1>[NH2:5][C:4]1[CH:6]=[C:7]([C:19]2[S:23][C:22]([C:24]3([OH:37])[CH2:29][CH2:28][CH:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]3)=[N:21][CH:20]=2)[CH:8]=[C:2]([CH3:1])[CH:3]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672361713-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 70926225Tert-butyl 4-(5-bromo-1,3-thiazol-2-yl)-4-hydroxycyclohexanecarboxylate

Product 1

HCID 58456118Tert-butyl 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-4-hydroxycyclohexanecarboxylate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a flask containing 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.6 g, 6.96 mmol), the product of Step 2 (2.52 g, 6.96 mmol), dicyclohexyl[2′,4′,6′-tri(propan-2-yl)biphenyl-2-yl]phosphane (0.33 g, 0.70 mmol), Pd2(dba)3 (0.32 g, 0.35 mmol), cesium carbonate (6.80 g, 20.9 mmol) was added a degassed mixture of dioxane (23 mL) and water (2.3 mL). The solution was evacuated and then purged with argon 5 times and then heated at 100° C. overnight. The reaction was then cooled to room temperature, diluted with ethyl aceate, washed with aqueous saturated sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated. Flash chromatography was used for purification to yield tert-butyl 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-4-hydroxycyclohexanecarboxylate. MS ESI: [M+H]+ m/z 389.

Workup

  1. customThe solution was evacuated
  2. custompurged with argon 5 times
  3. temperatureThe reaction was then cooled to room temperature
  4. additiondiluted with ethyl aceate
  5. washwashed with aqueous saturated sodium bicarbonate
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customFlash chromatography was used for purification

Sources & evidence

ORD record
ord-70b671e377ba4f7796edb6859dbd0b68
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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