Dimethylformamide → (+/-)-(trans)-5-Fluoro-2,3-dihydro-2,3-bis[(phenylmethoxy)methyl]-1,4-benzodioxin

HRID 1638554Notes

Reaction equation

HRID 1638554 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=1[OH:9].[C:10]1([CH2:16][O:17][CH2:18][C@@H:19](O)[C@H:20](O)[CH2:21][O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CN(C)C=O.C(=O)([O-])[O-].[Cs+].[Cs+]>C(OC(C)C)(C)C.O>[F:1][C:2]1[C:3]2[O:9][C@@H:19]([CH2:18][O:17][CH2:16][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C@H:20]([CH2:21][O:22][CH2:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[O:8][C:4]=2[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 677643-FluorocatecholHCID 7004210(+)-1,4-Di-O-benzyl-D-threitol

Product 1

HCID 13537380(+/-)-(trans)-5-Fluoro-2,3-dihydro-2,3-bis[(phenylmethoxy)methyl]-1,4-benzodioxin

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7914Diisopropyl EtherSolvent

Procedure

A mixture of 3-fluorobenzene-1,2-diol (5.12 g) and (R*,R*)-(±)-1,4-bis(phenylmethoxy)-2,3-butanediol, bis(4-methylbenzenesulphonate) (24.4 g) was stirred with dimethylformamide (D.M.F.) (160 ml) under a nitrogen stream for 45 min. Anhydrous cesium carbonate (13.0 g) was added and the mixture was heated to 150° under reflux for 18 hours. The dark brown mixture was cooled to 30° and diluted with di-isopropyl ether (370 ml) and water (320 ml). The layers were separated and the aqueous layer was re-extracted with di-isopropyl ether (150 ml then 100 ml). The extracts were sequentially washed with M hydrochloric acid (300 ml), 30% aqueous sodium chloride (100 ml) and were combined and evaporated in vacuo to a dark brown oil (12.6 g) which was dissolved in light petroleum-dichloromethane (3:1) (40 ml) and chromatographed over Sorbsil (126 g) using light petroleum-dichloromethane mixtures of gradually increasing polarity. Combination of appropriate fractions and evaporation of the solvents gave the title compound as a yellow oil (7.0 g), NMR τ (CDCl3) 2.6-2.8 (10H, m, Ph), 3.18-3.38 (3H, m, 6-H, 7-H, 8-H), 5.32-5.58 (4H, m, CH2Ph), 5.64 (2H, m, 2-H, 3-H), 6.06-6.32 (4H, m, CH2O).

Workup

  1. temperaturethe mixture was heated to 150°
  2. temperatureunder reflux for 18 hours
  3. temperatureThe dark brown mixture was cooled to 30°
  4. customThe layers were separated
  5. extractionthe aqueous layer was re-extracted with di-isopropyl ether (150 ml
  6. washThe extracts were sequentially washed with M hydrochloric acid (300 ml), 30% aqueous sodium chloride (100 ml)
  7. customevaporated in vacuo to a dark brown oil (12.6 g) which
  8. dissolutionwas dissolved in light petroleum-dichloromethane (3:1) (40 ml)
  9. customchromatographed over Sorbsil (126 g)
  10. temperatureof gradually increasing polarity
  11. customCombination of appropriate fractions and evaporation of the solvents

Sources & evidence

ORD record
ord-1d4c984a1a1c4eb4a3a5284633e9d3de
Source dataset
uspto-grants-1989_11
Patent number
US04880801

Reaction notes

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