Triphenylphosphine → [4-(Pyrazin-2-ylmethoxy)-phenyl]-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone

HRID 642205Notes

Reaction equation

HRID 642205 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:14][CH2:13][CH2:12][C@H:11]2[CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:9])=[CH:4][CH:3]=1.[N:21]1[CH:26]=[CH:25][N:24]=[CH:23][C:22]=1[CH2:27]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[N:21]1[CH:26]=[CH:25][N:24]=[CH:23][C:22]=1[CH2:27][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:14][CH2:13][CH2:12][C@H:11]2[CH2:15][N:16]2[CH2:17][CH2:18][CH2:19][CH2:20]2)=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 201734PyrazinemethanolHCID 5462977Diethyl azodicarboxylateHCID 11960316(4-hydroxy-phenyl)-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone

Product 1

HCID 11588685[4-(Pyrazin-2-ylmethoxy)-phenyl]-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanoneYield 1.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of (4-Hydroxy-phenyl)-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone (0.57 g, 2.0 mmol), pyrazin-2-yl-methanol [CAS 6705-33-5] (0.25 g, 2.3 mmol), and triphenylphosphine (0.57 g, 2.2 mmol) in THF (20 mL) is added DEAD (0.36 mL, 2.3 mmol). The mixture is stirred at room temperature overnight and partitioned between ethyl acetate and water. The aqueous phase is extracted with ethyl acetate (2×), and the combined organic phase is dried (Na2SO4) and concentrated. The crude material is purified by SCX chromatography followed by silica gel chromatography eluting with 20% (10% 2M MeOH/CH2Cl2)/80% CH2Cl2 to 70% (10% 2M MeOH/CH2Cl2)/30% CH2Cl2 to yield 12 mg of the title compound. MS (ES+) 367.3

Workup

  1. custompartitioned between ethyl acetate and water
  2. extractionThe aqueous phase is extracted with ethyl acetate (2×)
  3. dry with materialthe combined organic phase is dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe crude material is purified by SCX chromatography
  6. washeluting with 20% (10% 2M MeOH/CH2Cl2)/80% CH2Cl2 to 70% (10% 2M MeOH/CH2Cl2)/30% CH2Cl2

Sources & evidence

ORD record
ord-1d00b1a2b22b4c7fa34035716e2cef49
Source dataset
uspto-grants-2010_04
Patent number
US07696234B2

Reaction notes

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