Benzenesulfinic acid → (2RS,7S)-2-(benzenesulfonyl)-7-(4-fluorophenoxymethyl)oxepane

HRID 413578Notes

Reaction equation

HRID 413578 reaction equation
[C:1]1([S:7]([OH:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl-].[Cl-].[Ca+2].[F:13][C:14]1[CH:29]=[CH:28][C:17]([O:18][CH2:19][C@@H:20]([OH:27])[CH2:21][CH2:22][CH2:23][CH2:24][CH:25]=O)=[CH:16][CH:15]=1>C(Cl)Cl>[C:1]1([S:7]([CH:25]2[CH2:24][CH2:23][CH2:22][CH2:21][C@@H:20]([CH2:19][O:18][C:17]3[CH:28]=[CH:29][C:14]([F:13])=[CH:15][CH:16]=3)[O:27]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 12057Benzenesulfinic acidHCID 5284359Calcium ChlorideHCID 59064024(6S)-7-(4-fluorophenoxy)-6-hydroxyheptanal

Product 1

HCID 70026601(2RS,7S)-2-(benzenesulfonyl)-7-(4-fluorophenoxymethyl)oxepaneYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

25% HCl was added dropwise to sodium salt of benzenesulfinic acid (5 g, 30.5 mmol) until the solid dissolved. The reaction mixture was extracted with EtOAc, dried over Na2SO4 and concentrated to give benzenesulfinic acid (3.9 g, 90%). To an ice-cold mixture of benzene sulfinic acid (1.8 g, 12.4 mmol) and CaCl2, (1.4 g, 12.5 mmol) in dry methylene chloride (50 ml) was added dropwise a solution of (6S)-7-(4-fluorophenoxy)-6-hydroxy-heptanal (2 g, 8.3 mmol) in methylene chloride (10 ml). The reaction mixture was stirred for 3 hours and filtered through celite, and washed with methylene chloride. The combined organic layer was washed with saturated aqueous Na2CO3, water, brine and dried over Na2SO4. Solvent was removed under reduced pressure and the residue was purified by silica gel chromatography using EtOAC-hexane (1:6) as eluent to give (2RS,7S)-2-(benzenesulfonyl)-7-(4-fluorophenoxymethyl)oxepane (2.45 g, 80.8%); 1H-NMR (CDCl3, 200 Hz): δ 1.39-2.20 (m, 7H), 2.5 (m, 1H), 3.57-3.90 (m, 2H), 4.45 (m, 1H), 4.72 (dd, J=6.6, 12.0 Hz, 1H), 6.57-7.00 (m, 4H), 7.36-7.96 (m, 5H).

Workup

  1. filtrationfiltered through celite
  2. washwashed with methylene chloride
  3. washThe combined organic layer was washed with saturated aqueous Na2CO3, water, brine
  4. dry with materialdried over Na2SO4
  5. customSolvent was removed under reduced pressure
  6. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-3d08109c29d64ee6ac11cb4047d2d47c
Source dataset
uspto-grants-2003_05
Patent number
US06566538B1

Reaction notes

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