Phenol → (S)-tert-Butyl 2-(phenoxymethyl)pyrrolidine-1-carboxylate

HRID 2068656Notes

Reaction equation

HRID 2068656 reaction equation
[C:1]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][OH:14])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[C:15]1(O)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C(Cl)Cl.C1(C)C=CC=CC=1>[C:4]([O:3][C:1]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

7

Reactant 4

HCID 996PhenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 643448(S)-(-)-N-Boc-prolinol

Product 1

HCID 10636271(S)-tert-Butyl 2-(phenoxymethyl)pyrrolidine-1-carboxylateYield 59.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-(−)-1-Boc-2-pyrrolidine methanol (0.267 g, 1.33 mmol), phenol (0.38 g, 4.02 mmol) and triphenylphosphine (0.71 g, 2.71 mmol) in DCM (5 mL) was cooled in an ice-bath and a solution of diisopropyl azodicarboxylate (0.55 g, 2.71 mmol) in toluene (3 mL) was added. The ice-bath was removed and the reaction mixture was stirred at room temperature over the weekend. The mixture was diluted with ether and washed with sodium hydroxide (3 M), then brine, dried over sodium sulfate and evaporated. The resultant solid was suspended in ethyl acetate and cyclohexane and the resultant white crystalline solid was removed by filtration. The filtrate was evaporated and the crude material was purified by column chromatography using a 10 g Si II cartridge eluting with 10% ethyl acetate in cyclohexane to afford (S)-2-phenoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester as a clear oil (0.22 g).

Workup

  1. customThe ice-bath was removed
  2. additionThe mixture was diluted with ether
  3. washwashed with sodium hydroxide (3 M)
  4. dry with materialbrine, dried over sodium sulfate
  5. customevaporated
  6. customcyclohexane and the resultant white crystalline solid was removed by filtration
  7. customThe filtrate was evaporated
  8. customthe crude material was purified by column chromatography
  9. washeluting with 10% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-d90e4e2d30a2455a8b9027bf2066e62b
Source dataset
uspto-grants-2012_10
Patent number
US08299063B2

Reaction notes

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