Triphenylphosphine → (S)-Tert-butyl 2-(((5-bromopyridin-3-YL)oxy)methyl)azetidine-1-carboxylate

HRID 2305112Notes

Reaction equation

HRID 2305112 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.[C:32]([N:39]1[CH2:42][CH2:41][C@H:40]1[CH2:43][OH:44])([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].[Br:45][C:46]1[CH:47]=[C:48](O)[CH:49]=[N:50][CH:51]=1>C1COCC1>[Br:45][C:46]1[CH:47]=[C:48]([O:44][CH2:43][C@@H:40]2[CH2:41][CH2:42][N:39]2[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH:49]=[N:50][CH:51]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5995293-Bromo-5-hydroxypyridineHCID 5462977Diethyl azodicarboxylateHCID 10511797tert-butyl (2S)-2-(hydroxymethyl)azetidine-1-carboxylate

Product 1

HCID 10688713(S)-Tert-butyl 2-(((5-bromopyridin-3-YL)oxy)methyl)azetidine-1-carboxylateYield 47.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triphenylphosphine (4.01 g, 15.3 mmol) and DEAD (2.43 mL, 15.3 mmol) were dissolved in 30 mL of THF at 0° C., and the mixture was stirred for for 10 minutes. Samples of 1-BOC-2-(S)-azetidinemethanol (2.86 g, 15.3 mmol), prepared as described above, and 5-bromo-3-hydroxypyridine (1.505 g, 10.2 mmol) were added, and the reaction mixture was stirred for 40 hours at room temperature. The volatiles were removed under vacuum, and the residue was triturated with hexane. The hexane was removed, and the residue was chromatographed on a silica gel column, eluting with hexane:Et2O 10:1 to 10:2 to afford the title compound as a colorless oil (1.669 g). MS (CI/NH3) m/z 344 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.42 (s, 9H), 2.31 (m, 2H), 3.89 (m, 2H), 4.12 (m, 1H), 4.322 (m, 1H), 4.52 (m, 1H), 7.43 (m, 1H), 8.29 (m, 2H).

Workup

  1. additionwere added
  2. stirringthe reaction mixture was stirred for 40 hours at room temperature
  3. customThe volatiles were removed under vacuum
  4. customthe residue was triturated with hexane
  5. customThe hexane was removed
  6. customthe residue was chromatographed on a silica gel column
  7. washeluting with hexane:Et2O 10:1 to 10:2

Sources & evidence

ORD record
ord-9377abd2afd84c94900ea9c3a32b7030
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

Loading…