Cyclohexanol → HCID 58495607, compound

HRID 1190975Notes

Reaction equation

HRID 1190975 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH:9]1(O)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.C(P(CCCC)CCCC)CCC.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>CCOC(C)=O.O.C1COCC1.C1C=CC=CC=1>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 7966CyclohexanolHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 8198212-Chloro-5-hydroxypyridine

Product 1

HCID 58495607HCID 58495607, compoundYield 58%

Reagents, catalysts & solvents 4

HCID 241BenzeneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Under a nitrogen atmosphere add 6-chloro-pyridin-3-ol (2.5 g, 19.3 mmol), cyclohexanol (1.93 g, 19.3 mmol), tri-n-butylphosphine (5.07 g, 25.1 mmol), and ADDP (6.32 g, 25.1 mmol) to benzene (100 mL) and THF (10 mL) at 0° C. Stir the mixture at 0° C. for 1 h and at room temperature for 12 h. Dilute with EtOAc and water. Separate the layers and extract the aqueous layer with EtOAc. Wash the organic phase with water (30 mL) and brine (20 mL). Dry the organic phase over Na2SO4, filter, and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel (400 g) eluting with hexane/EtOAc (1:0 to 98:2 gradient) to obtain the desired intermediate as clear oil (1.8 g, 58%). MS (APCI+) m/z: 212 (M+H)+.

Workup

  1. waitat room temperature for 12 h
  2. customSeparate the layers
  3. extractionextract the aqueous layer with EtOAc
  4. washWash the organic phase with water (30 mL) and brine (20 mL)
  5. dry with materialDry the organic phase over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify the crude mixture by chromatography on silica gel (400 g)
  9. washeluting with hexane/EtOAc (1:0 to 98:2 gradient)

Sources & evidence

ORD record
ord-fa28a5bb752247e99a5b8c03ec6415c3
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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