3-Hydroxypyridine → HCID 68612157, compound

HRID 2095310Notes

Reaction equation

HRID 2095310 reaction equation
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC.[CH2:32]([O:39][C:40]1[CH:41]=[C:42]([CH:46]([CH:48]2[CH2:50][CH2:49]2)O)[CH:43]=[N:44][CH:45]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[OH:51][C:52]1[CH:53]=[N:54][CH:55]=[CH:56][CH:57]=1.N1(C2OC(N3CCCCC3)=NN=2)CCCCC1>C1(C)C=CC=CC=1>[CH2:32]([O:39][C:40]1[CH:45]=[N:44][CH:43]=[C:42]([C@H:46]2[CH2:48][C@@H:50]2[CH2:49][O:51][C:52]2[CH:53]=[N:54][CH:55]=[CH:56][CH:57]=2)[CH:41]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

7

Reactant 5

HCID 79713-HydroxypyridineHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 67317292HCID 67317292, compoundHCID 68613011HCID 68613011, compound

Product 1

HCID 68612157HCID 68612157, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

1,1′-(Azodicarbonyl)dipiperidine (237 mg, 0.94 mmol, 1.6 equiv.) was dissolved in 2 mL of toluene (dried with molecular sieve 3 Å) in a 10 mL round-bottom flask with a side neck. The flask was equipped with rubber septa and a magnetic stirrer. The atmosphere was exchanged with Ar (3 times), and the flask was cooled with an ice bath. Tri-n-butylphosphine (232 μL, 0.94 mmol, 1.6 equiv.) was added dropwise. The mixture was warmed to room temperature and stirred for 10 min. The resulting colorless solution was then added dropwise (via syringe) with ice cooling to a solution of (1S,2S)-2-[(5-(benzyloxy)-3-pyridyl]cyclopropylmethanol (50 mg, 0.59 mmol) and 3-hydroxypyridine (89 mg, 0.94 mmol, 1.6 equiv.) in a 25 mL round-bottom flask (equipped with a magnetic stirrer and an Ar balloon). The resulting mixture was warmed to room temperature and stirred for 6 h. Air was bubbled through the mixture with stirring for 1 h. Toluene was evaporated, and the residue was purified by CC on SiO2 (15×1.0 cm, EtOAc) to give the crude product, which was contaminated with a by-product, 2,5-di-(1-piperidinyl)-1,3,4-oxadiazole. This material was further purified by preparative HPLC in two portions (Supelco Discovery C18, 250×21.2 mm, 5 μm particle size, UV detection at 270 nm, flow rate 12.5 mL/min, gradient from 20% to 100% CH3CN in water within 40 min, then 100% CH3CN for 20 min; tR 22.7-24.0 min) to give a yellowish oil (125 mg, 64%). MS (EI) m/z 332 (M+, 67%).

Workup

  1. customThe flask was equipped with rubber septa and a magnetic stirrer
  2. temperaturethe flask was cooled with an ice bath
  3. customequipped with a magnetic stirrer
  4. temperatureThe resulting mixture was warmed to room temperature
  5. stirringstirred for 6 h
  6. customAir was bubbled through the mixture
  7. stirringwith stirring for 1 h
  8. customToluene was evaporated
  9. customthe residue was purified by CC on SiO2 (15×1.0 cm, EtOAc)
  10. customto give the crude product, which
  11. customThis material was further purified by preparative HPLC in two portions (Supelco Discovery C18, 250×21.2 mm, 5 μm particle size, UV detection at 270 nm, flow rate 12.5 mL/min, gradient from 20% to 100% CH3CN in water within 40 min
  12. wait100% CH3CN for 20 min

Sources & evidence

ORD record
ord-d5205bf5a09d45fe9be4420cc23e7abb
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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