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Chlorotrimethylsilane → (2R,3R)-1-(Dimethylamino)-3-(3-methoxyphenyl)-2-methylpentan-3-ol HCl

HRID 2394978
Notes
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Reaction equation

HRID 2394978 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[CH:4]=1.[CH3:11][N:12]([CH3:20])[CH2:13][CH:14]([CH3:19])[C:15](=[O:18])[CH2:16][CH3:17].[Cl-].[NH4+].C[Si](C)(C)[Cl:25]>O1CCCC1.CCOCC.CC(=O)CC.O>[ClH:25].[CH3:11][N:12]([CH3:20])[CH2:13][CH:14]([CH3:19])[C:15]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[CH:4]=1)([OH:18])[CH2:16][CH3:17]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

10

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 169713-BromoanisoleHCID 25517Ammonium ChlorideHCID 30487291-(Dimethylamino)-2-methyl-3-pentanoneHCID 5462224Magnesium

Product 1

HCID 18974517(2R,3R)-1-(Dimethylamino)-3-(3-methoxyphenyl)-2-methylpentan-3-ol HCl
Yield 47.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6569Methyl Ethyl KetoneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

27.0 g (1.11 mole) of magnesium turnings were stirred in 150 ml tetrahydrofuran and 207.6 g (1.11 mole) 1-bromo-3-methoxy-benzene, dissolved in 400 ml tetrahydrofuran, were added drop-wise. The mixture was heated for one hour under reflux and was subsequently cooled to a temperature between 5° C. and 10° C. 128.30 g (0.89 mole) (RS)-1-dimethylamino-2-methyl-pentan-3-one, dissolved in 400 ml tetrahydrofuran, were added drop-wise at this temperature. The reaction mixture was allowed to stand and was subsequently cooled again to a temperature between 5° C. and 10° C. After adding 300 ml of 20 weight % ammonium chloride solution, the mixture was diluted with 400 ml ether. After phase separation the batch was extracted twice with ether, dried over sodium sulphate and the solvent was removed by distillation. The residue obtained was taken up in 3.2 l 2-butanone and treated with 120.60 g (1.11 mole) trimethylchlorosilane and 20 ml water. 121.5 g of hydrochloride (2) (38% theoretical) with a melting point of 198°-199° C. were obtained. 2nd step:

Workup

  1. additionwere added drop-wise
  2. temperatureThe mixture was heated for one hour
  3. temperatureunder reflux
  4. temperaturewas subsequently cooled to a temperature between 5° C. and 10° C
  5. additionwere added drop-wise at this temperature
  6. temperaturewas subsequently cooled again to a temperature between 5° C. and 10° C
  7. customAfter phase separation the batch
  8. extractionwas extracted twice with ether
  9. dry with materialdried over sodium sulphate
  10. customthe solvent was removed by distillation
  11. customThe residue obtained

Sources & evidence

ORD record
ord-b993ec200c4b4d7b8bdf662dfaa98480
Source dataset
uspto-grants-1998_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05811582

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes