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tert-Butyl methyl ether → (S)-1-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethanol

HRID 1922640
Notes
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Reaction equation

HRID 1922640 reaction equation
[CH3:1]OC(C)(C)C.C[Zn]C.[Br:10]/[CH:11]=[C:12]1/[C@H:13]2[C@:17]([CH3:21])([CH2:18][CH2:19][CH2:20]/1)[C:16]([CH:22]=[O:23])=[CH:15][CH2:14]2>C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C.[C@@H]1(NS(C(F)(F)F)(=O)=O)CCCC[C@H]1NS(C(F)(F)F)(=O)=O.C(OCC)(=O)C>[Br:10]/[CH:11]=[C:12]1\[CH2:20][CH2:19][CH2:18][C@@:17]2([CH3:21])[C@H:13]\1[CH2:14][CH:15]=[C:16]2[C@@H:22]([OH:23])[CH3:1]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 15413tert-Butyl methyl etherHCID 59456515(3aR,4E,7aS)-4-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-7a-methyl-3H-indene-1-carbaldehyde2×HCID 178477796HCID 178477796, compound

Product 1

HCID 59456520(S)-1-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethanolYield 100%

Reagents, catalysts & solvents 3

HCID 11090167
(1R)-trans-N,N'-1,2-Cyclohexanediylbis(1,1,1-trifluoromethanesulfonamide)
Catalyst
HCID 178460666HCID 178460666, compoundCatalyst
HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

(1R)-trans-N,N′-1,2-cyclohexanediylbis(1,1,1-trifluoromethanesulfonamide) (2.3 mg, 0.006 mmol) was placed in a reaction vessel. After replacing the atmosphere with nitrogen, t-butyl methyl ether (0.03 ml) was added thereto and dissolved. To the solution, tetraisopropoxy titanium (0.0177 ml, 0.06 mmol) was added at room temperature, and the resulting mixture was heated at 50° C. for 30 minutes. After cooling to room temperature, dimethylzinc (1.0 M in heptane, 0.12 ml, 0.12 mmol) was added thereto. The obtained reaction mixture was added to (3aR,4E,7aS)-4-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-7a-methyl-3H-indene-1-carbaldehyde (Compound 29: 15.3 mg, 0.06 mmol). After stirring the reaction solution at room temperature for 1 hour, ethyl acetate (30 ml) was added thereto, and the resulting mixture was washed with 2N hydrochloric acid, saturated brine and with saturated aqueous sodium hydrogen carbonate solution, respectively. The organic layer was dried over sodium sulfate, and the solvent was evaporated to obtain the reaction mixture. The reaction mixture was purified by preparative TCL to obtain (S)-1-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethanol (18.4 mg, 100%). The spectrum data thereof agreed with the data described in Example 4.

Workup

  1. additionwas added
  2. dissolutiondissolved
  3. temperatureAfter cooling to room temperature
  4. customThe obtained reaction mixture
  5. washthe resulting mixture was washed with 2N hydrochloric acid, saturated brine and with saturated aqueous sodium hydrogen carbonate solution
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. customthe solvent was evaporated
  8. customto obtain the reaction mixture
  9. customThe reaction mixture was purified by preparative TCL

Sources & evidence

ORD record
ord-3695cd263fa04fa5bcbd7f6e0258f1a9
Source dataset
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08173824B2

Reaction notes

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