Dichloromethane → 7-Bromo-2-[(R)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-quinoline

HRID 2285392Notes

Reaction equation

HRID 2285392 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([OH:14])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1.FC(F)(F)S(O[Si:21](C)([CH3:23])[CH3:22])(=O)=O.N1[C:32]([CH3:33])=[CH:31]C=CC=1C.OP([O-])(O)=O.[K+].Cl[CH2:42]Cl>O>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([O:14][Si:21]([C:32]([CH3:31])([CH3:33])[CH3:42])([CH3:23])[CH3:22])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 79372,6-LutidineHCID 65367Trimethylsilyl triflateHCID 516951Monobasic potassium phosphateHCID 86706048(R)-1-(7-Bromoquinolin-2-yl)ethanol2×

Product 1

HCID 867096827-Bromo-2-[(R)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-quinolineYield 94%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of (R)-1-(7-bromo-quinolin-2-yl)-ethanol (2.52 g, 10 mmol) in dichloromethane (55 mL) was cooled to 0° C. before adding trimethylsilyl trifluoromethanesulfonate (2.7 mL, 12 mmol) and 2,6-lutidine (1.75 mL, 15 mmol). The reaction mixture was stirred for 2 h then treated with a saturated solution of potassium phosphate monobasic in water. The aqueous layer was extracted with dichloromethane. The extracts were combined, dried over anhydrous magnesium sulfate and the volatiles were evaporated. A second batch was made in the same way from (R)-1-(7-bromo-quinolin-2-yl)-ethanol (375 mg, 1.49 mmol) using the same proportions of reagents. After the same work up the crudes were combined, and purified by silica gel chromatography using a stepwise gradient of iso-hexanes/ethyl acetate 99:1 to 24:1 to yield the title product (3.96 g, 94%) as a solid. 1H NMR (300 MHz, CDCl3) δ 0.02 (s, 3H), 0.12 (s, 3H), 0.94 (s, 9H), 1.54 (d, J=6.5 Hz, 3H), 5.12 (q, J=6.5 Hz, 1H), 7.61 (dd, J=8.7, 1.8 Hz, 1H), 7.69 (d, J=8.5 Hz, 1H), 7.75 (d, J=8.5 Hz, 1H), 8.15 (d, J=8.5 Hz, 1H), 8.24 (s, 1H).

Workup

  1. extractionThe aqueous layer was extracted with dichloromethane
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customthe volatiles were evaporated
  4. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-1d5318790c854e47bc5d46e2206428bb
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

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