Triphenylphosphine → (3S)-1-(2-pyridinylmethyl)-3-piperidinyl (2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylate

HRID 412650Notes

Reaction equation

HRID 412650 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([OH:14])[CH2:9]1.[O:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[C:16]1[N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]1[C:30](O)=[O:31].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[O:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[C:16]1[N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]1[C:30]([O:14][C@H:10]1[CH2:11][CH2:12][CH2:13][N:8]([CH2:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH2:9]1)=[O:31]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 12050655(2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylic acidHCID 53657319HCID 53657319, compound

Product 1

HCID 57262118(3S)-1-(2-pyridinylmethyl)-3-piperidinyl (2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylateYield 54.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(3R)-1-(2-Pyridinylmethyl)-3-piperidinol (117 mg) [see Preparation 35] was added to a stirred solution of (2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylic acid (150 mg) [see Preparation 3], triphenylphosphine (192 mg) and diethyl azodicarboxylate (0.115 ml) in dry tetrahydrofuran (6 ml). The reaction mixture was stirred at reflux for 16 hours, after which time the solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and 0.5M aqueous hydrochloric acid. The aqueous layer was then basified with 15% sodium hydroxide and the product extracted with ethyl acetate. The organic layer was then separated, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with 98:2, by volume, ethyl acetate:methanol to afford (3S)-1-(2-pyridinylmethyl)-3-piperidinyl (2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylate (140 mg) as a yellow oil. The hydrochloride salt was prepared by dissolving the title compound in ethyl acetate and bubbling hydrogen chloride gas through the solution, to afford the title compound as a white solid.

Workup

  1. temperatureat reflux for 16 hours
  2. customafter which time the solvent was removed under reduced pressure
  3. customthe residue partitioned between ethyl acetate and 0.5M aqueous hydrochloric acid
  4. extractionthe product extracted with ethyl acetate
  5. customThe organic layer was then separated
  6. dry with materialdried over magnesium sulphate
  7. customthe solvent removed under reduced pressure
  8. customThe crude product was purified by column chromatography on silica gel eluting with 98:2, by volume, ethyl acetate

Sources & evidence

ORD record
ord-a50398f6683e46638810aa03fae1c04e
Source dataset
uspto-grants-2003_05
Patent number
US06562964B1

Reaction notes

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