Triphenylphosphine → tert-Butyl(2R,5S)-5-azido-2-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]piperidine-1-carboxylate

HRID 255350Notes

Reaction equation

HRID 255350 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH2:10][C:9](=[O:12])[N:8]([CH2:13][CH2:14][C@H:15]3[CH2:20][CH2:19][C@@H:18](O)[CH2:17][N:16]3[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:7]=2[CH:29]=1)#[N:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.C1(P([N:77]=[N+:78]=[N-:79])(C2C=CC=CC=2)=O)C=CC=CC=1>C1COCC1.C(OCC)(=O)C>[N:77]([C@@H:18]1[CH2:17][N:16]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[C@@H:15]([CH2:14][CH2:13][N:8]2[C:7]3[CH:29]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][C:6]=3[O:11][CH2:10][C:9]2=[O:12])[CH2:20][CH2:19]1)=[N+:78]=[N-:79]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 199401P,P-Diphenylphosphinic azideHCID 5363146Diisopropyl azodicarboxylateHCID 66774129tert-butyl (2R,5R)-2-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]-5-hydroxypiperidine-1-carboxylate2×

Product 1

HCID 86642656tert-Butyl(2R,5S)-5-azido-2-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]piperidine-1-carboxylateYield 36.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl (2R,5R)-2-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]-5-hydroxypiperidine-1-carboxylate (Intermediate 185, crude, 0.8 g) in THF (20 mL) were successively added triphenylphosphine (1.30 g), diisopropylazodicarboxylate (1 mL) and diphenyl phosphoryl azide (0.90 g). After 4 hours, the reaction was diluted with ethyl acetate, washed with saturated solution of sodium hydrogen carbonate (NaHCO3) and brine, dried over sodium sulfate and concentrated. Chromatography on silica gel with a gradient of 0-5% methanol in methylene chloride gave 0.31 g of product.

Workup

  1. washwashed with saturated solution of sodium hydrogen carbonate (NaHCO3) and brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-f9df51f3c36746999a07b3e237f148b9
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

Loading…