4-Toluenesulfonyl chloride → HCID 21971397, compound

HRID 1955263Notes

Reaction equation

HRID 1955263 reaction equation
[H-].[Na+].[C:3]1([CH2:9][C:10]#N)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[CH2:13][C@H:14](C)[CH2:15][O:16]S(C1C=CC(C)=CC=1)(=O)=O.Br[CH2:29][C@H:30]([CH3:33])[CH2:31]O.C1(C)C=CC(S(Cl)(=O)=[O:41])=CC=1.C1(C2(C#N)CC(C)C2)C=CC=CC=1.C1(C2(C(O)=O)CC(C)C2)C=CC=CC=1.O=S(Cl)Cl.C(O)C=C>N1C=CC=CC=1>[C:3]1([C:9]2([C:10]([O:16][CH2:15][CH:14]=[CH2:13])=[O:41])[CH2:31][CH:30]([CH3:33])[CH2:29]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

11

Reactant 9

HCID 73974-Toluenesulfonyl chlorideHCID 7858Allyl AlcoholHCID 8794PhenylacetonitrileHCID 24386Thionyl ChlorideHCID 24758Sodium hydrideHCID 10441885(R)-(-)-3-Bromo-2-methyl-1-propanolHCID 21971385HCID 21971385, compoundHCID 23294920HCID 23294920, compoundHCID 86755865HCID 86755865, compound

Product 1

HCID 21971397HCID 21971397, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

The title compound was prepared in an analogous manner to that in Example 29. NaH (60% dispersion in mineral oil, 77.8 mmol) was reacted at room temperature with phenylacetonitrile and (R)-3-bromo-O-p-toluenesulfonyl-2-methyl-1-propanol that was prepared by reacting (R)-(-)-3-bromo-2-methyl-1-propanol (33 mmol) with p-toluenesulfonyl chloride (39 mmol) in pyridine for 17 h. The afforded 1-phenyl-3-methylcyclobutanecarbonitrile contained 75% of the cis isomer and 25% of the trans isomer. In order to separate the two isomers, the allylester of the acid was prepared. 1-Phenyl-3-methylcyclobutanecarboxylic acid (24 mmol) was refluxed with neat SOCl2 (25 mL) for 1 h. SOCl2 was then evaporated, the residue was dissolved in toluene and allylalcohol (26 mmol) and pyridine (26 mmol) were added. The mixture was stirred overnight to give allyl 1-phenyl-3-methylcyclobutanecarboxylate that was chromatographed on silica gel containing 2% AgNO3 using a gradient of hexane up to hexane-EtOAc 95:5 as eluent. 1.3 g of allyl 1-phenyl-3-trans-methylcyclobutanecarboxylate was obtained. The allyl ester was then hydrolysed with KOH as described above. The obtained product contained 10% of the cis isomer. The total yield was 0.66 g (11%); 1H NMR (CDCl3) δ 1.09 (d, 3H), 2.15-2.30 (m, 1H), 2.38-2.48 (m, 2H), 2.65-2.75 (m, 2H), 7.21-7.41 (m, 5H).

Workup

  1. customThe title compound was prepared in an analogous manner to that in Example 29
  2. customwas prepared
  3. customfor 17 h
  4. customIn order to separate the two isomers
  5. customSOCl2 was then evaporated
  6. dissolutionthe residue was dissolved in toluene

Sources & evidence

ORD record
ord-4b48c84310d346ebb3eba210060db0b8
Source dataset
uspto-grants-2000_09
Patent number
US06124354

Reaction notes

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