Water → (E,1R,3aR,7aS)-4-(bromomethylene)-octahydro-1-{(R)-1-hydroxyethyl}-7a-methyl-1H-indene-1-ol

HRID 1922636Notes

Reaction equation

HRID 1922636 reaction equation
[Br:1]/[CH:2]=[C:3]1/[C@H:4]2[C@:8]([CH3:12])([CH2:9][CH2:10][CH2:11]/1)/[C:7](=[CH:13]/[CH3:14])/[CH2:6][CH2:5]2.CS(N)(=O)=[O:17].CC[C@H]1[C@H]2C[C@H]([C@H](OC3C4C(=CC=CC=4)C(O[C@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C(OC)C=C4)N(CC2)C1.S([O-])([O-])=O.[Na+].[Na+].[OH2:84]>C(OCC)(=O)C.C(O)(C)(C)C>[Br:1]/[CH:2]=[C:3]1/[C@H:4]2[C@:8]([CH3:12])([CH2:9][CH2:10][CH2:11]/1)[C@:7]([C@H:13]([OH:17])[CH3:14])([OH:84])[CH2:6][CH2:5]2

Participants

8

Reactant 5

HCID 962Water2×HCID 24437Sodium SulfiteHCID 72879MethanesulfonamideHCID 510036741-((1R)-((2R,4R,5S)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)-4-((1R)-((2R,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)phthalazineHCID 59456521(1E,3aR,4E,7aS)-4-(bromomethylene)-1-ethylidene-octahydro-7a-methyl-1H-indene2×

Product 1

HCID 59456516(E,1R,3aR,7aS)-4-(bromomethylene)-octahydro-1-{(R)-1-hydroxyethyl}-7a-methyl-1H-indene-1-olYield 85.3%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (1E,3aR,4E,7aS)-4-(bromomethylene)-1-ethylidene-octahydro-7a-methyl-1H-indene (Compound 21: 19.2 mg, 0.07524 mmol), methanesulfonamide (21.5 mg, 0.2257 mmol) and AD-mix-α (105 mg), t-butanol (0.4 ml) and water (0.4 ml) were added, and the reaction mixture was stirred at room temperature for 48 hours. Sodium sulfite (113 mg) was added thereto and the resulting mixture was stirred at room temperature for 1 hour. Ethyl acetate and water were added thereto, and the resulting mixture was extracted 3 times with ethyl acetate. The organic layer was washed with 2 M aqueous potassium hydroxide solution (1 ml) and saturated brine (2.5 ml), and dried over sodium sulfate, followed by evaporation under reduced pressure. The obtained crude product (23.2 mg) was purified by flash column chromatography to obtain (E,1R,3aR,7aS)-4-(bromomethylene)-octahydro-1-{(R)-1-hydroxyethyl}-7a-methyl-1H-indene-1-ol (18.6 mg, 85.3%).

Workup

  1. additionwere added
  2. stirringthe resulting mixture was stirred at room temperature for 1 hour
  3. extractionthe resulting mixture was extracted 3 times with ethyl acetate
  4. washThe organic layer was washed with 2 M aqueous potassium hydroxide solution (1 ml) and saturated brine (2.5 ml)
  5. dry with materialdried over sodium sulfate
  6. customfollowed by evaporation under reduced pressure
  7. customThe obtained crude product (23.2 mg)
  8. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-fbc14994483648fc8efe3fd339f15b47
Source dataset
uspto-grants-2012_05
Patent number
US08173824B2

Reaction notes

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