1-Naphthol → 1,1-Dimethylethyl 3-[(1-naphthalenyloxy)methyl]-1-pyrrolidinecarboxylate

HRID 912743Notes

Reaction equation

HRID 912743 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4]1.[C:15]1(O)[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][CH:16]=1.C(P(CCCC)CCCC)CCC.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1(C)C=CC=CC=1.O1CCCC1>[C:23]1([O:1][CH2:2][CH:3]2[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4]2)[C:24]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:20]=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 70051-NaphtholHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 5237175tert-Butyl 3-(hydroxymethyl)pyrrolidine-1-carboxylate

Product 1

HCID 674164501,1-Dimethylethyl 3-[(1-naphthalenyloxy)methyl]-1-pyrrolidinecarboxylateYield 49.9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1.0 g (4.9 mmol) of 1,1-dimethylethyl 3-(hydroxymethyl)-1-pyrrolidinecarboxylate (described in WO 0066557), 0.95 g (6.4 mmol) of 1-naphthalenol and 1.4 g (6.9 mmol) of tri-n-butylphosphine in 40 ml of toluene and 20 ml of tetrahydrofuran, cooled under nitrogen by means of an ice bath, is admixed dropwise with a solution of 1.74 g (6.9 mmol) of ADDP. The reaction mixture is allowed to return to ambient temperature and stirring is continued for 24 hours. The mixture is filtered and the precipitate is rinsed with toluene. It is evaporated to dryness. The residue is taken up in dichloromethane and washed with a 1M aqueous sodium hydroxide solution. It is dried over sodium sulfate and evaporated to dryness. The residue is purified by chromatography on a silica gel column, eluting with dichloromethane and then with a 98/2 mixture of dichloromethane and methanol, to give 0.80 g of product in colorless oil form.

Workup

  1. customto return to ambient temperature
  2. filtrationThe mixture is filtered
  3. washthe precipitate is rinsed with toluene
  4. customIt is evaporated to dryness
  5. washwashed with a 1M aqueous sodium hydroxide solution
  6. dry with materialIt is dried over sodium sulfate
  7. customevaporated to dryness
  8. customThe residue is purified by chromatography on a silica gel column
  9. washeluting with dichloromethane
  10. additionwith a 98/2 mixture of dichloromethane and methanol

Sources & evidence

ORD record
ord-ef2b098853ae4cb8b13685c03e9b30a2
Source dataset
uspto-grants-2011_09
Patent number
US08026258B2

Reaction notes

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