Pyridine → (3aS,7S,7aS)-rel-6-(2,4-dimethoxy-benzyl)-7-(2-fluoro-phenyl)-7-methyl-hexahydro-2,4-dioxa-5-thia-6-aza-indene 5-oxide

HRID 2178198Notes

Reaction equation

HRID 2178198 reaction equation
[CH3:1][O:2][C:3]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:4]=1[CH2:5][NH:6][C@@:7]([C@H:16]1[CH2:20][O:19][CH2:18][C@H:17]1[OH:21])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[F:15])[CH3:8].N1C=CC=CC=1.[S:34](Cl)(Cl)=[O:35]>ClCCl>[CH3:1][O:2][C:3]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:4]=1[CH2:5][N:6]1[C@@:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[F:15])([CH3:8])[C@@H:16]2[C@@H:17]([CH2:18][O:19][CH2:20]2)[O:21][S:34]1=[O:35]

Participants

5

Reactant 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 70654454rel-(3S,4S)-4-[(S)-1-(2,4-dimethoxy-benzylamino)-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ol

Product 1

HCID 70654406(3aS,7S,7aS)-rel-6-(2,4-dimethoxy-benzyl)-7-(2-fluoro-phenyl)-7-methyl-hexahydro-2,4-dioxa-5-thia-6-aza-indene 5-oxideYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under a dry atmosphere of argon, a solution of rel-(3S,4S)-4-[(S)-1-(2,4-dimethoxy-benzylamino)-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ol (6.8 g, 18.1 mmol) in pyridine (7.32 ml, 90.5 mmol) and dichloromethane (120 ml) was cooled to −77° C. The colorless solution was treated dropwise with thionyl chloride (2.15 g, 18.1 mmol) over about 10 minutes while the temperature rose to −73° C. After removal of the cooling bath the reaction mixture was allowed to reach room temperature. For the workup, the reaction mixture was diluted with dichloromethane (150 ml) and washed consecutively with hydrochloric acid (1N) and a saturated solution of sodium hydrogencarbonate. The organic layer was dried over sodium sulphate and evaporated. The (3aS,7S,7aS)-rel-6-(2,4-dimethoxy-benzyl)-7-(2-fluoro-phenyl)-7-methyl-hexahydro-2,4-dioxa-5-thia-6-aza-indene 5-oxide (7.24 g, 95% yield) was obtained as a white solid. MS (ISP): m/z=422.0 [M+H]+.

Workup

  1. customrose to −73° C
  2. customAfter removal of the cooling bath the reaction mixture
  3. customto reach room temperature
  4. additionFor the workup, the reaction mixture was diluted with dichloromethane (150 ml)
  5. washwashed consecutively with hydrochloric acid (1N)
  6. dry with materialThe organic layer was dried over sodium sulphate
  7. customevaporated

Sources & evidence

ORD record
ord-a79556d3b172416ca5bc96bd3e33e48f
Source dataset
uspto-grants-2015_06
Patent number
US09067924B2

Reaction notes

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