Triphenylphosphine → (3R)-1-t-butoxycarbonyl-3-[4-(imidazol-1-yl)phenoxy]piperidine

HRID 1609812Notes

Reaction equation

HRID 1609812 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([OH:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:15]1([C:20]2[CH:25]=[CH:24][C:23](O)=[CH:22][CH:21]=2)[CH:19]=[CH:18][N:17]=[CH:16]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([O:14][C:23]2[CH:24]=[CH:25][C:20]([N:15]3[CH:19]=[CH:18][N:17]=[CH:16]3)=[CH:21][CH:22]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 823151-(p-Hydroxyphenyl)imidazoleHCID 1514398(R)-1-Boc-3-hydroxypiperidineHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 69367678(3R)-1-t-butoxycarbonyl-3-[4-(imidazol-1-yl)phenoxy]piperidineYield 6.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of (3R)-1-t-butoxycarbonyl-3-hydroxypiperidine (4.10 g, 17.8 mmol), 4-(imidazol-1-yl)phenol (4.4 g, 1.5 eq.), triphenylphosphine (1.5 eq., 7.10 g), DMF (80 mL) was added DEAD (1.5 eq., 4.33 mL). The resulting reaction mixture were stirred at room temperature for two days. The solvent was evaporated, the residue was diluted with ethyl acetate, washed with 1N NaOH (45 mL×3), water and brine, and evaporated in vacuo. Purification by flash column chromatography on silical gel with gradient 1-3% methanol in CH2Cl2 gave (3R)-1-t-butoxycarbonyl-3-[4-(imidazol-1-yl)phenoxy]piperidine (420 mg, 1.19 mmol), which was treated with trifluoroacetic acid/CH2Cl2 (1:1) from 0° C. to ambient temperature for 2 hours. The solvents were evaporated. The residue was diluted with CH2Cl2, and washed with 1N HCl (10 mL). The aqueous phase was extracted with CH2Cl2 to remove by-product. The aqueous phase was re-adjusted to pH 9.5 to 10.0 with 1N NaOH. Extraction with CH2Cl2 (60 mL×3) and evaporation of the solvent in vacuo gave (3R)-3-[4-(imidazol-1-yl)phenoxy]piperidine (62 mg) as an oil.

Workup

  1. customThe resulting reaction mixture
  2. customThe solvent was evaporated
  3. additionthe residue was diluted with ethyl acetate
  4. washwashed with 1N NaOH (45 mL×3), water and brine
  5. customevaporated in vacuo
  6. customPurification by flash column chromatography on silical gel with gradient 1-3% methanol in CH2Cl2

Sources & evidence

ORD record
ord-b6876b22f18d438cbfba5c61959069cb
Source dataset
uspto-grants-2006_01
Patent number
US06982259B2

Reaction notes

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