(Diethylamino)sulfur trifluoride → 3-(2-Fluoropropan-2-yl)-5-((triisopropylsilyloxy)methyl)pyridine

HRID 2071075Notes

Reaction equation

HRID 2071075 reaction equation
[CH:1]([Si:4]([CH:20]([CH3:22])[CH3:21])([CH:17]([CH3:19])[CH3:18])[O:5][CH2:6][C:7]1[CH:8]=[C:9]([C:13](O)([CH3:15])[CH3:14])[CH:10]=[N:11][CH:12]=1)([CH3:3])[CH3:2].C(N(S(F)(F)[F:29])CC)C>C(Cl)Cl>[F:29][C:13]([C:9]1[CH:10]=[N:11][CH:12]=[C:7]([CH2:6][O:5][Si:4]([CH:20]([CH3:22])[CH3:21])([CH:17]([CH3:19])[CH3:18])[CH:1]([CH3:3])[CH3:2])[CH:8]=1)([CH3:15])[CH3:14]

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 686702432-(5-((Triisopropylsilyloxy)methyl)pyridin-3-yl)propan-2-ol

Product 1

HCID 686709273-(2-Fluoropropan-2-yl)-5-((triisopropylsilyloxy)methyl)pyridineYield 38.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To 2-(5-((triisopropylsilyloxy)methyl)pyridin-3-yl)propan-2-ol (1.1 g, 3.4 mmol) in DCM (30 mL) at −78° C. was added diethylaminosulfur trifluoride (DAST) (0.67 mL, 5.1 mmol) and stirred at the same temperature for 1 hr, then warmed to 0° C. for 3 hrs. The resulting mixture was quenched with MeOH and saturated aqueous NaHCO3. The mixture was extracted with EtOAc three times and dried with anhydrous NaSO4, filtered and concentrated to dryness. Careful purification by flash chromatography (silica gel, hexanes/EtOAc) gave the desired fluoride (3-(2-fluoropropan-2-yl)-5-((triisopropylsilyloxy)methyl)pyridine) as a light yellow solid (0.43 g). 1H NMR (CDCl3): d: 1.127 (d, J=6.3 Hz, 18H), 1.204 (m, 3H), 1.712 (s, 3H), 1.786 (s, 3H), 4.922 (s, 2H), 7.781 (s, 1H), 8.566 (s, 2H). 3-(2-fluoropropan-2-yl)-5-((triisopropylsilyloxy)methyl)pyridine was deprotected with excess aqueous HF in THF to provide (5-(2-fluoropropan-2-yl)pyridin-3-yl)methanol as a white solid. (5-(2-fluoropropan-2-yl)pyridin-3-yl)methanol was then oxidized to 5-(2-fluoropropan-2-yl)nicotinaldehyde using standard Swern Oxidation conditions.

Workup

  1. customThe resulting mixture was quenched with MeOH and saturated aqueous NaHCO3
  2. extractionThe mixture was extracted with EtOAc three times
  3. dry with materialdried with anhydrous NaSO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customCareful purification by flash chromatography (silica gel, hexanes/EtOAc)

Sources & evidence

ORD record
ord-faba7e46b92d460e9a5c8d92a6e428c4
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

Loading…