p-Chloroacetophenone and
NaCN are reacted together to give the corresponding
cyanohydrin (cf
Strecker synthesis),
CID:12439573. The cyano group is then hydrated in acid to the corresponding amide, p-chloroatrolactamide,
CID:15255544 (4). The amide group is then further hydrolyzed with a 2nd equivalent of water in concentrated lye to p-chloroatrolactic acid, [4445-13-0] (5). Esterification to Ethyl p-chloroatrolactate [100126-96-3](6). Finally,
nucleophilic addition a couple of equivalents of MeMgI are added to the ester give Phenaglycodol (7) crystals.
A mixed
Pinacol coupling rxn between 4-chloroacetophenone [99-91-2] and
acetone with magnesium activated with a small amount of
trimethylsilyl chloride gave a 40% yield of phenglycodol.
Notes
See "Novel trifluoromethyl derivatives of substituted diols" U.S. patent 3,134,819 also.
^Usdin E, Efron DH, U.S. National Institute of Mental Health (1972).
Psychotropic drugs and related compounds. National Institute of Mental Health; [for sale by the Supt. of Docs., U.S. Govt. Print. Off., Washington.
ISBN9780080255101.