1-Azido-4-fluorobenzene → (S)-tert-Butyl 2-(4-(1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)phenyl)morpholine-4-carboxylate

HRID 710244Notes

Reaction equation

HRID 710244 reaction equation
[N:1]([C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][CH:5]=1)=[N+:2]=[N-:3].[C:11]([C:13]1[CH:18]=[CH:17][C:16]([C@@H:19]2[O:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20]2)=[CH:15][CH:14]=1)#[CH:12]>C(N(CC)C(C)C)(C)C.[Cu]I>[F:10][C:7]1[CH:8]=[CH:9][C:4]([N:1]2[CH:12]=[C:11]([C:13]3[CH:14]=[CH:15][C:16]([C@@H:19]4[O:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20]4)=[CH:17][CH:18]=3)[N:3]=[N:2]2)=[CH:5][CH:6]=1

Participants

5

Reactant 2

HCID 108879741-Azido-4-fluorobenzeneHCID 89689402(S)-tert-butyl 2-(4-ethynylphenyl)morpholine-4-carboxylate

Product 1

HCID 118412982(S)-tert-Butyl 2-(4-(1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)phenyl)morpholine-4-carboxylateYield 28.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 81531DiisopropylethylamineSolvent

Procedure

1-Azido-4-fluorobenzene (24 mg, 0.174 mmol) was dissolved in N,N-diisopropylethylamine (0.75 ml), then (S)-tert-butyl 2-(4-ethynylphenyl)morpholine-4-carboxylate (50 mg, 0.175 mmol) was added followed by copper(I) iodide (33 mg, 0.174 mmol). The mixture was stirred at room temperature for 3 h. The green mixture was concentrated on the rotavap, silica gel (0.5 g) was added and after short grinding the mixture was put on a silica gel column for purification. Flash chromatography (5 g silica gel, 30% ethyl acetate in heptane) yielded a white solid (21 mg, 28%). MS (ISP): 369.1 ([M-tBu+H]+), 425.2 ([M+H]+).

Workup

  1. concentrationThe green mixture was concentrated on the rotavap, silica gel (0.5 g)
  2. additionwas added
  3. customafter short grinding the mixture
  4. customwas put on a silica gel column for purification

Sources & evidence

ORD record
ord-60a29c3938d6495ba2ccafdd9d507156
Source dataset
uspto-grants-2015_11
Patent number
US09181230B2

Reaction notes

Loading…