(1r,3s)-3-Acetyl-2,2-dimethylcyclobutane-1-carboxylic acid → (1R,3S)-3-(1-hydroxy-1-methylethyl)-2,2-dimethylcyclobutanecarboxylic acid

HRID 558015Notes

Reaction equation

HRID 558015 reaction equation
[CH3:1][C@@H](CC)C(OC[C@@H]1CC(=C(C)C)C1(C)C)=O.[C:18]([C@H:21]1[CH2:24][C@@H:23]([C:25]([OH:27])=[O:26])[C:22]1([CH3:29])[CH3:28])(=[O:20])[CH3:19].C[Mg]Cl>>[OH:20][C:18]([C@H:21]1[CH2:24][C@@H:23]([C:25]([OH:27])=[O:26])[C:22]1([CH3:29])[CH3:28])([CH3:1])[CH3:19]

Participants

4

Reactant 3

HCID 11008353(1r,3s)-3-Acetyl-2,2-dimethylcyclobutane-1-carboxylic acidHCID 11299404[(R)-2,2-Dimethyl-3-(1-methylethylidene)cyclobutyl]methyl (S)-2-methylbutanoateHCID 178418332HCID 178418332, compound

Product 1

HCID 11480888(1R,3S)-3-(1-hydroxy-1-methylethyl)-2,2-dimethylcyclobutanecarboxylic acid

Procedure

A method for making [(R)-2,2-dimethyl-3-(1-methylethylidene)cyclobutyl]methyl (S)-2-methylbutanoate (2), said method comprising (or consisting essentially of or consisting of) reacting (1R,3S)-3-acetyl-2,2-dimethylcyclobutanecarboxylic acid [(cis)-pinononic acid] with methyl magnesium chloride to form (1R,3S)-3-(1-hydroxy-1-methylethyl)-2,2-dimethylcyclobutanecarboxylic acid (3) or reacting (1R,3S)-3-acetyl-2,2-dimethylcyclobutanecarboxylic acid [(cis)-pinononic acid] with methyl lithium, and then methyl magnesium chloride to form (1R,3S)-3-(1-hydroxy-1-methylethyl)-2,2-dimethylcyclobutanecarboxylic acid (3); reacting (1R,3S)-3-(1-hydroxy-1-methylethyl)-2,2-dimethylcyclobutanecarboxylic acid (3) with phosphorus oxychloride to form (1R,5S)-4,4,6,6-tetramethyl-3-oxabicyclo[3.1.1]heptan-2-one (4); reacting (1R,5S)-4,4,6,6-tetramethyl-3-oxabicyclo[3.1.1]heptan-2-one (4) with p-toluenesulfonic acid to form (R)-2,2-dimethyl-3-(1-methlethylidene)cyclobutanecarboxylic acid (5); reacting (R)-2,2-dimethyl-3-(1-methlethylidene)cyclobutanecarboxylic acid (5) with lithium aluminum hydride to form [(R)-(−)-2,2-dimethyl-3-(1-methylethylidene)cyclobutyl]methanol [(R)-maconelliol] (6), and reacting [(R)-(−)-2,2-dimethyl-3-(1-methylethylidene)cyclobutyl]methanol (6) with oxalyl chloride and (S)-2-methylbutanoic acid to form [(R)-2,2-dimethyl-3-(1-methylethylidene)cyclobutyl]methyl (S)-2-methylbutanoate [(R)-maconelliyl (S)-2-methylbutanoate] (2).

Sources & evidence

ORD record
ord-e428e9293a624d3ebd846470f1fd5f7b
Source dataset
uspto-grants-2011_11
Patent number
US08062651B1

Reaction notes

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