Tetrahydrofuran → HCID 86680141, compound

HRID 1915943Notes

Reaction equation

HRID 1915943 reaction equation
[CH3:1]C(C)([O-])C.[K+].C1COCC1.[CH3:12][N:13]1[C:17]([N:18]2[CH2:24][C:23](=O)[CH2:22][C@@H:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:20][CH2:19]2)=[C:16]([N+:34]([O-:36])=[O:35])[CH:15]=[N:14]1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1>[CH2:1]=[C:23]1[CH2:24][N:18]([C:17]2[N:13]([CH3:12])[N:14]=[CH:15][C:16]=2[N+:34]([O-:36])=[O:35])[CH2:19][CH2:20][C@H:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:22]1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 23665647Potassium tert-butoxideHCID 86680142HCID 86680142, compound

Product 1

HCID 86680141HCID 86680141, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 1140TolueneSolvent2×

Procedure

Methyl triphenylphosphonium bromide (3.09 g, 8.49 mmol) was suspended in toluene (25 mL). Potassium tert-butoxide (1.0 mol/L) in THF (7.07 mL, 7.074 mmol) was added and the mixture turned bright yellow. It was stirred at room temperature for 4 h, then tert-butyl N-[(4S)-1-(2-methyl-4-nitro-pyrazol-3-yl)-6-oxo-azepan-4-yl]carbamate (1000 mg, 2.83 mmol) (second eluting peak in the chiral separation) in 5 mL toluene was added. The mixture was stirred at RT for 30 min, quenched with saturated ammonium chloride, and extracted with EA 3×. The combined organic layers were concentrated and the residue was purified via silica gel column chromatography (0-100% EA/heptane) to give tert-butyl N-[(4R)-6-methylene-1-(2-methyl-4-nitro-pyrazol-3-yl)azepan-4-yl]carbamate (699 mg, 70%).

Workup

  1. additionwas added
  2. stirringThe mixture was stirred at RT for 30 min
  3. customquenched with saturated ammonium chloride
  4. extractionextracted with EA 3×
  5. concentrationThe combined organic layers were concentrated
  6. customthe residue was purified via silica gel column chromatography (0-100% EA/heptane)

Sources & evidence

ORD record
ord-99755228ce2f4e51a4e6ada4da4174e8
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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