Triphenylphosphine → (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methyl ester

HRID 859207Notes

Reaction equation

HRID 859207 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:29][O:30][C:31]([C@H:33]1[CH2:37][C:36](=[O:38])[N:35]([C:39]2[CH:44]=[CH:43][C:42](O)=[CH:41][CH:40]=2)[CH2:34]1)=[O:32].N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[CH3:29][O:30][C:31]([C@H:33]1[CH2:37][C:36](=[O:38])[N:35]([C:39]2[CH:44]=[CH:43][C:42]([O:6][CH2:5][C:4]3[CH:7]=[CH:8][CH:9]=[C:2]([F:1])[CH:3]=3)=[CH:41][CH:40]=2)[CH2:34]1)=[O:32]

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 13097Triphenylphosphine OxideHCID 680083-Fluorobenzylic alcoholHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 785701HCID 785701, compound

Product 1

HCID 68614551(S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methyl esterYield 68.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution 14.23 g (110.6 mmol) of 3-fluoro-benzylalcohol and 27.19 g (108.8 mmol) of triphenylphosphine in 150 ml of tetrahydrofurane is added dropwise within 50 min under a nitrogen atmosphere at 0° C. to a solution of 23.65 g (100.5 mmol) of (S)-1-(4-hydroxy-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester and 21.62 g (100.5 mmol) of diisopropyl azodicarboxylate in 200 ml of tetrahydrofurane. The mixture is left to warm to RT and stirring is continued for 18 hours. For the working-up, the mixture is evaporated under reduced pressure. The solid residue is triturated in 400 ml of ether to leave a white solid mainly consisting of the product and triphenylphosphinoxide. After filtration, the solid material is triturated in 100 ml of cold methanol to yield 23.5 g (68% of theory) of (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methyl ester as a white solid [MS: m/e=344 (M+H)+] together with traces of triphenylphosphine and diisopropyl hydrazodicarboxylate.

Workup

  1. waitThe mixture is left
  2. customthe mixture is evaporated under reduced pressure
  3. customThe solid residue is triturated in 400 ml of ether
  4. customto leave a white solid
  5. filtrationAfter filtration
  6. customthe solid material is triturated in 100 ml of cold methanol

Sources & evidence

ORD record
ord-96b066f86b834166adb16b88d05ed2ee
Source dataset
uspto-grants-2006_12
Patent number
US07151111B2

Reaction notes

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