Tributylphosphine → HCID 68611430, compound

HRID 2095313Notes

Reaction equation

HRID 2095313 reaction equation
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC.[CH2:32]([O:39][CH2:40][C@H:41]1[CH2:43][C@@H:42]1[C:44]1[CH:45]=[C:46]([OH:50])[CH:47]=[N:48][CH:49]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[C:51]([O:55][C:56]([N:58]1[CH2:61][CH2:60][C@H:59]1[CH2:62]O)=[O:57])([CH3:54])([CH3:53])[CH3:52]>C1(C)C=CC=CC=1>[C:51]([O:55][C:56]([N:58]1[CH2:61][CH2:60][C@H:59]1[CH2:62][O:50][C:46]1[CH:47]=[N:48][CH:49]=[C:44]([C@H:42]2[CH2:43][C@@H:41]2[CH2:40][O:39][CH2:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:45]=1)=[O:57])([CH3:54])([CH3:52])[CH3:53]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 10511797tert-butyl (2S)-2-(hydroxymethyl)azetidine-1-carboxylateHCID 68613132HCID 68613132, compound

Product 1

HCID 68611430HCID 68611430, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

1,1′-(Azodicarbonyl)dipiperidine (207 mg, 0.82 mmol, 1.6 equiv.) was dissolved in 2.0 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. Tributylphosphine (203 μL, 0.82 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 5-[(1S,2S)-2-(benzyloxymethyl)cyclopropyl]-3-pyridinol (131 mg, 0.51 mmol) and 1-(tert-butoxycarbonyl)-2(S)-azetidinylmethanol (154 mg, 0.82 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 overnight. Air was bubbled through the mixture for 2 h. The solvent was evaporated, and the residue was purified by CC on SiO2 (15×1.0 cm, EtOAc) to give the crude product, which was further purified by preparative HPLC (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 28.5-30.9 min) to give a colorless oil (170 mg, 79%). MS (EI) m/z 424 (M+, 0.5%).

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 overnight
  6. customAir was bubbled through the mixture for 2 h
  7. customThe solvent was evaporated
  8. customthe residue was purified by CC on SiO2 (15×1.0 cm, EtOAc)
  9. customto give the crude product, which
  10. customwas further purified by preparative HPLC (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
  11. wait100% CH3CN for 20 min

Sources & evidence

ORD record
ord-3a6a9edac81c45c584d3cb06654c54e3
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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