Cyclohexanecarboxylic acid, 3-hydroxy-, methyl ester, (1S,3R)- → HCID 23658346, compound

HRID 2233323Notes

Reaction equation

HRID 2233323 reaction equation
[C:1]1([C:7]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:11][N:10]=[C:9]([O:19][CH:20]3[CH2:25][CH2:24][CH2:23][C@H:22]([C:26]([O:28]C)=[O:27])[CH2:21]3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(P(C2C=CC=CC=2)(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)C=CC=CC=1.O[C@@H]1CCC[C@H](C(OC)=O)C1.C1(C2C(C3C=CC=CC=3)=CN=C(O)N=2)C=CC=CC=1.N(C(OC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)=O)=NC(OC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)=O>O1CCCC1.CN(C)C=O>[C:1]1([C:7]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:11][N:10]=[C:9]([O:19][CH:20]3[CH2:25][CH2:24][CH2:23][C@H:22]([C:26]([OH:28])=[O:27])[CH2:21]3)[N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 5

HCID 58952956Cyclohexanecarboxylic acid, 3-hydroxy-, methyl ester, (1S,3R)-HCID 86631154HCID 86631154, compoundHCID 86631155HCID 86631155, compoundHCID 86631156HCID 86631156, compoundHCID 178517622HCID 178517622, compound

Product 1

HCID 23658346HCID 23658346, compoundYield 4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

Methyl (1S)-3-(4,5-diphenylpyrimidin-2-yloxy)cyclohexanecarboxylate 1.5 g (2.12 mmol) of diphenylperfluorodecylphosphine were added to a solution of 280 mg (1.76 mmol) of methyl (1S,3R)-3-hydroxycyclohexanecarboxylate in 2 ml of tetrahydrofuran. After 30 minutes, 525 mg (2.12 mmol) of 4,5-diphenylpyrimidin-2-ol and 2 ml of tetrahydrofuran were added, and the mixture was again stirred for 30 minutes. A solution of 1.77 g (2.12 mmol) of bis(perfluorononyl) azodicarboxylate in 2 ml of tetrahydrofuran was slowly added dropwise (exothermic reaction) and stirred at room temperature for 2 hours. It was not possible to convert the suspension into a solution by adding 1 ml of dimethylformamide. The reaction mixture was filtered with suction (precipitate corresponds to 408 mg of 4,5-diphenylpyrimidin-2-ol). The filtrate was filtered twice through a FluoroFlash cartridge and washed with methanol/water=4/1, and the filtrate was concentrated. The residue was separated on a silica gel column (heptane/ethyl acetate, 10 minutes 100% heptane, gradient from 0% to 45% ethyl acetate in 45 minutes). 28 mg (4%) of the desired product were obtained.

Workup

  1. custom(exothermic reaction)
  2. stirringstirred at room temperature for 2 hours
  3. filtrationThe reaction mixture was filtered with suction (precipitate corresponds to 408 mg of 4,5-diphenylpyrimidin-2-ol)
  4. filtrationThe filtrate was filtered twice through a FluoroFlash cartridge
  5. washwashed with methanol/water=4/1
  6. concentrationthe filtrate was concentrated
  7. customThe residue was separated on a silica gel column (heptane/ethyl acetate, 10 minutes 100% heptane, gradient from 0% to 45% ethyl acetate in 45 minutes)

Sources & evidence

ORD record
ord-0fbf874eded94472802e5c1d31d84337
Source dataset
uspto-grants-2010_05
Patent number
US07709494B2

Reaction notes

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