Triethylsilane → HCID 10452233, compound

HRID 1767109Notes

Reaction equation

HRID 1767109 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[CH3:10][N:11]([CH3:30])[C:12]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:17][CH2:16][CH:15]([CH2:18]O[Si](C)(C)C)[CH2:14][CH2:13]1.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C([SiH](CC)CC)C.[OH-].[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][O:7][CH2:18][CH:15]2[CH2:14][CH2:13][C:12]([N:11]([CH3:10])[CH3:30])([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:17][CH2:16]2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 12052TriethylsilaneHCID 14798Sodium HydroxideHCID 65367Trimethylsilyl triflateHCID 680234-FluorobenzaldehydeHCID 21113404HCID 21113404, compound

Product 1

HCID 10452233HCID 10452233, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Under argon, 4-fluorobenzaldehyde (149 mg, 1.2 mmol) and dimethyl(1-phenyl-4-trimethylsilanyloxymethylcyclohexyl)amine (306 mg, 1 mmol) were dissolved in abs. DCM (20 ml) and cooled to 0° C. Trimethylsilyl triflate (387 μl, 2 mmol) was added dropwise at 0° C. and the mixture was stirred for 60 min at this temperature, after which triethylsilane (319 μl, 2 mmol) was added dropwise at 0° C. With slow heating to RT, the mixture was stirred overnight. For the work-up, DCM (10 ml) and 1 M NaOH (5 ml) were added and the mixture was stirred vigorously for 15 min. The organic phase was separated off, washed with 1 M NaOH (2×2 ml) and with water (1×2 ml), dried, filtered and concentrated. The residue was purified by chromatography on silica gel [40 g of silica gel 60; eluent: 600 ml of EE/MeOH (1:1) and 600 ml of MeOH/conc. NH3 (400:1)]. The two diastereoisomers of [4-(4-fluorobenzyloxymethyl)-1-phenylcyclohexyl]dimethylamine were isolated (17 mg of less polar diastereoisomer (yellow oil) and 106 mg of more polar diastereoisomer (yellow oil)). 75 mg of the more polar diastereoisomer were dissolved in 2-butanone (2 ml), with heating, chlorotrimethylsilane (83.4 μl) was added dropwise at RT and the mixture was stirred for 2 h. The solvent was completely distilled off and the residue was covered with a layer of dry ether and mechanically detached from the wall of the flask. The resulting solid was filtered off with suction, washed with ether (4×2 ml) and dried to give 79 mg of the hydrochloride of the more polar diastereoisomer of [4-(4-fluorobenzyloxymethyl)-1-phenylcyclohexyl]-dimethylamine (greyish-white solid, m.p. 176-181° C.).

Workup

  1. stirringthe mixture was stirred overnight
  2. stirringthe mixture was stirred vigorously for 15 min
  3. customThe organic phase was separated off
  4. washwashed with 1 M NaOH (2×2 ml) and with water (1×2 ml)
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography on silica gel [40 g of silica gel 60; eluent: 600 ml of EE/MeOH (1:1) and 600 ml of MeOH/conc. NH3 (400:1)]

Sources & evidence

ORD record
ord-6c4c2d94eedb46058bdd3957e6c26af1
Source dataset
uspto-grants-2007_06
Patent number
US07232847B2

Reaction notes

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