Water → [3(R)-t-Butyldimethylsiloxy, 1-Hydroxybutyl]-2,5-Dichloropyridine

HRID 974228Notes

Reaction equation

HRID 974228 reaction equation
Br[C:2]1[C:3]([Cl:9])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[O:10]([C@H:18]([CH3:22])[CH2:19][CH:20]=[O:21])[Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12].O>C(OC(C)C)(C)C>[O:10]([C@H:18]([CH3:22])[CH2:19][CH:20]([C:2]1[C:3]([Cl:9])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1)[OH:21])[Si:11]([C:14]([CH3:15])([CH3:16])[CH3:17])([CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 962WaterHCID 11117121Butanal, 3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-, (R)-HCID 129015963-Bromo-2,5-dichloropyridine

Product 1

HCID 15008387[3(R)-t-Butyldimethylsiloxy, 1-Hydroxybutyl]-2,5-DichloropyridineYield 72%

Reagents, catalysts & solvents 1

HCID 7914Diisopropyl EtherSolvent3×

Conditions

Temperature
-70 °C

Procedure

To a cooled (-70° C.) solution of n-butylithium (129.3 mL of 1.18 M hexanes solution, 0.153 mol) in isopropyl ether was added a solution of 3-bromo-2,5-dichloropyridine (36.45 g, 0.161 mol) in isopropyl ether (225 mL) over a period of 30 minutes. The resulting white suspension was then treated with a solution of 3(R)-t-butyldimethylsiloxybutyraldehyde (34.14 g, 0.169 mol) in isopropyl ether (106 mL) and allowed to stir for an additional 30 minutes at -70° C. followed by warming to room temperature. After the addition of 480 mL of water, the biphasic mixture was separated and the organic layer was extracted with isopropyl ether (2×200 mL). The combined organic layers were washed once with water, heated with decolorizing carbon [G-60 DARCO (trademark)] filtered through diatomateous earth [Celite (trademark)] and condensed on a rotary evaporator. The resulting hazy yellow liquid was heated at 80° C. under high vacuum overnight to yield the desired product (mixture of diastereomers) as an amber oil (40.52 g, 72%): Rf 0.36 (25% Et2O in hexanes); 1H NMR (60 MHz, CDCl3) δ 0.1 (s, 6H), 0.82 (s, 9H), 1.18 (m, 3H), 1.72 (m, 2H), 4.16 (m, 1H), 4.42 (m, 1H), 5.10 (m, 1H), 7.92 (d, 1H, J=2.6 Hz), 8.13 (d, 1H, J=2.6 Hz).

Workup

  1. temperatureby warming to room temperature
  2. customthe biphasic mixture was separated
  3. extractionthe organic layer was extracted with isopropyl ether (2×200 mL)
  4. washThe combined organic layers were washed once with water
  5. temperatureheated with decolorizing carbon [G-60 DARCO (trademark)]
  6. filtrationfiltered through diatomateous earth [Celite (trademark)] and condensed on a rotary evaporator
  7. temperatureThe resulting hazy yellow liquid was heated at 80° C. under high vacuum overnight

Sources & evidence

ORD record
ord-2797dd624ecc4daba45088d7ee7d28ab
Source dataset
uspto-grants-1991_11
Patent number
US05068333

Reaction notes

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