Water → [(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl4-bromobenzenesulfonate

HRID 859998Notes

Reaction equation

HRID 859998 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]3[O:15][CH2:14][C@H:13]([CH2:16][OH:17])[O:12][C:8]3=2)[N:3]=1.[S:18](Cl)([C:21]1[CH:27]=[CH:26][C:24]([Br:25])=[CH:23][CH:22]=1)(=[O:20])=[O:19].C(N(CC)CC)C.O>C1(C)C=CC=CC=1.C(O)(C)C.CN(C1C=CC=CN=1)C>[Br:25][C:24]1[CH:26]=[CH:27][C:21]([S:18]([O:17][CH2:16][C@@H:13]2[O:12][C:8]3=[C:9]4[C:4](=[CH:5][CH:6]=[C:7]3[O:15][CH2:14]2)[N:3]=[C:2]([CH3:1])[CH:11]=[CH:10]4)(=[O:20])=[O:19])=[CH:22][CH:23]=1

Participants

8

Reactant 4

HCID 962WaterHCID 7396p-Bromobenzenesulfonyl chlorideHCID 8471TriethylamineHCID 11183845[(2S)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]-methanol

Product 1

HCID 20624762[(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl4-bromobenzenesulfonateYield 76.9%

Reagents, catalysts & solvents 3

HCID 218852-DimethylaminopyridineCatalystHCID 1140TolueneSolvent2×HCID 3776IsopropanolSolvent

Procedure

A solution of [(2S)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]-methanol (4.0 g, 17.3 mmol), brosyl chloride (4.86 g, 19.0 mmol), dimethylamino pyridine (20 mg, 0.16 mmol) and triethylamine (3.62 mL, 25.8 mmol) in toluene (40 mL) was stirred at 60° C. for 6 hours. The reaction mixture was cooled to room temperature then water (20 mL) was added. After 30 minutes, the two layers were separated. The organic layer was extracted with 8% NaHCO3 (20 mL) and H2O (20 mL), dried over Na2SO4, filtered and concentrated in vacuo. The solid obtained was dissolved in isopropyl alcohol (50 mL) and toluene (10 mL) at 80° C., cooled to room temperature over 1 hour then filtered, washed with (5:1) IPA:toluene (2×5 mL) and dried in a vacuum oven to give 5.99 g (76.9%) of the title compound as an off-white solid: 13C NMR (CDCl3) δ 157.9, 144.3, 138.1, 134.7, 132.9, 129.7, 129.6, 129.0, 122.4, 121.7, 121.3, 118.8, 70.7, 67.6, 64.5, 25.4

Workup

  1. customthe two layers were separated
  2. extractionThe organic layer was extracted with 8% NaHCO3 (20 mL) and H2O (20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe solid obtained
  7. filtrationthen filtered
  8. washwashed with (5:1) IPA
  9. dry with materialtoluene (2×5 mL) and dried in a vacuum oven

Sources & evidence

ORD record
ord-d3fbac83a50f47e0b0eb2ecb0dfedc86
Source dataset
uspto-grants-2006_12
Patent number
US07153849B2

Reaction notes

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