Benzenesulfinic acid → (2RS,6S)-6-benzenesulfonyl-2-(4-fluorophenoxymethyl)-tetrahydropyran

HRID 413574Notes

Reaction equation

HRID 413574 reaction equation
[C:1]1([S:7]([OH:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl-].[Ca+2].[Cl-].[F:13][C:14]1[CH:29]=[CH:28][C:17]([O:18][CH2:19][C@H:20]2[O:25][CH:24](OC)[CH2:23][CH2:22][CH2:21]2)=[CH:16][CH:15]=1>C(Cl)Cl>[C:1]1([S:7]([C@@H:24]2[O:25][CH:20]([CH2:19][O:18][C:17]3[CH:16]=[CH:15][C:14]([F:13])=[CH:29][CH:28]=3)[CH2:21][CH2:22][CH2:23]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 20588441(2RS,6S)-6-(4-fluorophenoxymethyl)-2-methoxytetrahydropyran

Product 1

HCID 20588442(2RS,6S)-6-benzenesulfonyl-2-(4-fluorophenoxymethyl)-tetrahydropyranYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

25% HCl was added dropwise to benzenesulfinic acid sodium salt (2.0 g), till the solid dissolved. This mixture was extracted with ethyl acetate (30 ml), dried (Na2SO4) and concentrated to give benzenesulfinic acid (1.5 g). To an ice-cooled mixture of benzenesulfinic acid (1.48 g, 10.5 mmol) and calcium chloride (1.15 g, 10.5 mmol) in dry CH2Cl2 a solution of (2RS,6S)-6-(4-fluorophenoxymethyl)-2-methoxytetrahydropyran (0.5 g, 2.1 mmol) in dry CH2Cl2 (5 ml) was added. The reaction mixture was stirred for 4 h, filtered through celite and washed with CH2Cl2. The combined organic layer was washed with saturated aqueous Na2CO3, water, brine and dried (Na2SO4). The solvent was removed under vacuum and the residue was purified on a silica gel column using light petroleum-ethyl acetate (4:1) as eluent to afford pure (2RS,6S)-6-benzenesulfonyl-2-(4-fluorophenoxymethyl)-tetrahydropyran (0.5 g, 70%) as a viscous liquid. TLC:ethyl acetate-light petroleum (1:3), Rf=0.4. 1H NMR (CDCl3, 200 MHz): 8 1.5 (m, 2H), 1.75-2.0 (m, 2H), 2.2-2.4 (m, 1H), 2.6-2.8 (m, 1H), 3.75-3.9 (m, 2H), 4.65 (d, 1H) m, 1H), 6.7-7.0 (m, 4H), 7.5-7.7 (m, 3H), 7.95 (d, J=5.4 Hz, 2H).

Workup

  1. additionwas added
  2. filtrationfiltered through celite
  3. washwashed with CH2Cl2
  4. washThe combined organic layer was washed with saturated aqueous Na2CO3, water, brine
  5. dry with materialdried (Na2SO4)
  6. customThe solvent was removed under vacuum
  7. customthe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-da011fe455d944498181ef7ea87594b8
Source dataset
uspto-grants-2003_05
Patent number
US06566538B1

Reaction notes

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