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

HRID 2242942Notes

Reaction equation

HRID 2242942 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-984e193e0d34494d815f675beac57146
Source dataset
uspto-grants-2010_03
Patent number
US07674805B2

Reaction notes

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