Methoxymethyl-triphenylphosphonium chloride → HCID 86680156, compound

HRID 1915958Notes

Reaction equation

HRID 1915958 reaction equation
[Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[K+].[F:30][C:31]([F:53])([F:52])[C:32]([NH:34][C@H:35]1[C:41](=O)[CH2:40][CH2:39][N:38]([C:43]2[N:44]([CH3:51])[N:45]=[CH:46][C:47]=2[N+:48]([O-:50])=[O:49])[CH2:37][CH2:36]1)=[O:33]>C(OCC)C.C1COCC1>[F:30][C:31]([F:53])([F:52])[C:32]([NH:34][C@H:35]1[C:41](=[CH:2][O:3][CH3:4])[CH2:40][CH2:39][N:38]([C:43]2[N:44]([CH3:51])[N:45]=[CH:46][C:47]=2[N+:48]([O-:50])=[O:49])[CH2:37][CH2:36]1)=[O:33]

Participants

6

Reactant 3

HCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 23665647Potassium tert-butoxideHCID 86680157HCID 86680157, compound

Product 1

HCID 86680156HCID 86680156, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-15 °C

Procedure

(Methoxymethyl)triphenylphosphonium chloride (5.59 g, 15.8 mmol) (dried on vacuum overnight before use) was suspended in ethyl ether (65 mL). The suspension was cooled to −15° C. Potassium tert-butoxide (1.0 mol/L) in THF (12.6 mL, 12.6 mmol) was added slowly and the bright orange suspension was stirred at −25° C. to −10° C. for 1 h while the color persisted. 2,2,2-Trifluoro-N-[(4R)-1-(2-methyl-4-nitro-pyrazol-3-yl)-5-oxo-azepan-4-yl]acetamide (1.38 g, 3.95 mmol) was dissolved in THF (12 mL) and added to the ylide at −15° C. The mixture was slowly allowed to warm to room temperature and stirred overnight then 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 2,2,2-trifluoro-N-[(4R)-5-(methoxymethylene)-1-(2-methyl-4-nitro-pyrazol-3-yl)azepan-4-yl]acetamide.

Workup

  1. additionadded to the ylide at −15° C
  2. temperatureto warm to room temperature
  3. stirringstirred overnight
  4. customthen quenched with saturated ammonium chloride
  5. extractionextracted with EA 3×
  6. concentrationThe combined organic layers were concentrated
  7. customthe residue was purified via silica gel column chromatography (0-100% EA/heptane)

Sources & evidence

ORD record
ord-66f25881f4f44bca82bdc5065a2f1225
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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