2
M HCl (1 mL) and then concentrated under reduced
pressure. The residue was distilled to give the title compound
as a colourless liquid (11.0 g, 90%), bp 87 °C at 22 mbar
6), 3.40-3.21 (2 H, m), 2.92 (6 H, s), and 2.16-2.10 (2 H,
m).
(E)-4-Phenyl-but-3-en-2-ol (11). (E)-4-Phenyl-but-3-en-
2-one (10) (14.82 g, 101.3 mmol) and 2-propanol (100 mL)
were charged to a glass-lined 600-mL Parr hydrogenation
vessel. The solution was degassed by charging to 150 psi
4
18
1
(
Lit. 89-90 °C at 16 mmHg), H NMR (400 MHz, CDCl
δ 7.39-7.25 (5 H, m), 4.89 (1 H, q, J 7), 1.90 (1 H, br) and
.49 (3 H, d, J 7); GC purity 99.1%, retention time 12.08
3
)
1
min (Zebron ZB5, 30 m × 0.25 mm, 60 °C for 5 min, ramp
N , stirring, and then venting (×5). Separately, a catalyst
2
to 200 °C at 10 °C/min, hold for 5 min).
solution was prepared by dissolving 1a (38 mg, 0.05 mmol,
endo-Norborneol (5). Norcamphor 6 (80.0 g, 726.2
mmol) and 2-propanol (400 mL) were charged to a glass-
lined 2-L hydrogenation vessel. The solution was degassed
S/C 2000) and potassium tert-butoxide (1 M in tert-butyl
alcohol, 0.5 mL) in toluene (4 mL) in a Schlenk flask under
nitrogen. This solution was then added to the vessel. A
hydrogen atmosphere was established by charging to 150
by charging to 100 psi N
2
, stirring, and then venting (×5).
The mixture was then stirred under nitrogen pressure (100
psi) for 30 min. During this time the contents were cooled
to 20 °C. The mixture was then depressurised to about 5 psi
psi H
2
and venting. The vessel was charged again to 150 psi
1
H
2
, and the mixture was stirred at 20 °C for 2.5 h ( H NMR
analysis showed complete conversion). The solvent was
evaporated, and the residue was filtered through a pad of
silica (12 g), eluting with ethyl acetate/heptane (1:4; 200 mL).
The solution was concentrated to give a brown oil which
was distilled under reduced pressure to give the title
compound 11 as a colourless liquid (12.28 g, 82%), bp 126
2
N pressure, and a suspension of 1a (50 mg, 0.07 mmol) in
degassed, anhydrous 2-propanol (5 mL) was added, followed
by potassium tert-butoxide (1 M in tert-butyl alcohol, 3.3
mL). A hydrogen atmosphere was established by charging
2
to 140 psi H and venting. The vessel was charged again to
1
40 psi H , and the mixture was stirred at 20 °C, maintaining
2
19
1
°
(
1
C at 26 mbar (Lit. 80-85 °C at 0.5 mmHg), H NMR
400 MHz, CDCl ) δ 7.39-7.22 (5 H, m), 6.57 (1 H, d, J
6), 6.26 (1 H, dd, J 16, 8), 4.49 (1 H, m), 1.62 (1 H, br s)
the hydrogen pressure between 140 and 100 psi until
hydrogen uptake ceased (922 min, ∼22h). The reaction
mixture was then concentrated under reduced pressure to give
the title compound 5 (83.2 g, >100%, 96% de) that was of
3
and 1.37 (3 H, d, J 7); GC purity 97.5%; retention time 16.90
min (Zebron ZB5, 30 m × 0.25 mm, 60 °C for 5 min, ramp
to 200 °C at 10 °C/min, hold for 5 min).
1
sufficient purity for subsequent reactions. H NMR (400
MHz, CDCl
J 4), 2.16 (1 H, apparent t, J 4), 2.00-1.85 (2 H, m), 1.65-
.55 (1H, m), 1.40-1.25 (3H, m), 0.86 (1H, t, J 3.4), 0.82
1H, t, J 3.4). The exo isomer is readily identified as a broad
doublet at δ 3.75 (1H).
-Dimethylamino-1-phenylpropan-1-ol hydrochloride
9 HCl salt). Dimethylaminopropiophenone (8) (13.23 g,
4.7 mmol) was dissolved in 2-propanol (70 mL) and
charged to a glass-lined 600-mL Parr hydrogenation vessel.
The solution was degassed by charging to 150 psi N , stirring,
3
) δ 4.25-3.90 (1 H, m), 2.25 (1 H, apparent t,
3
,5,5-Trimethyl-cyclohex-2-enol (Isophorol) (15). Iso-
phorone 14 (16.5 g, 120 mmol) and 2-propanol (120 mL)
were charged to a glass-lined 600-mL Parr hydrogenation
vessel. The solution was degassed by charging to 150 psi
1
(
N
2
, stirring, and then venting (×5). Separately, potassium
3
tert-butoxide (1 M in tert-butyl alcohol, 1.2 mL) was added
to a suspension of 2a (47 mg, 0.06 mmol, S/C 2000) in
(
7
2
-propanol (8 mL) in a Schlenk tube under nitrogen, and
the mixture was stirred for 20 min. The catalyst solution was
then added to the hydrogenation vessel, and a hydrogen
2
and then venting (×3). During this time the contents were
atmosphere was established by charging to 150 psi H
venting. The vessel was charged again to 150 psi H
2
and
, the
heated to 30 °C, and the catalyst solution was prepared. 2a
2
(11.7 mg, 0.015 mmol, S/C 5000) was added to a 10-mL
contents were heated to 30 °C, and the mixture was stirred
Schlenk tube. A nitrogen atmosphere was established by
1
for 21 h. H NMR analysis showed >99% conversion. The
evacuation and refilling with nitrogen (×3). Degassed
reaction mixture was neutralised with 1 M HCl (1.2 mL)
and evaporated under reduced pressure. The residue was
distilled to give the title compound 15 as a colourless liquid
2-propanol (3 mL) and potassium tert-butoxide (1 M in tert-
butyl alcohol, 0.15 mL) were added, and the mixture was
heated in an oil bath to 70 °C (external temperature) until a
clear, brown solution was obtained. The pressure vessel was
2
0
(
11.8 g, 70%), bp 86 °C at 28 mbar (Lit. 95-100 °C at 25
1
mmHg), H NMR (400 MHz, CDCl
3
) δ 5.42 (1 H, br), 4.24
charged to 150 psi H
added, and the vessel was charged again to 150 psi H
2
and vented, the catalyst solution was
. The
(1 H, m), 1.85 (1 H, d, J 16), 1.76 (1 H, dd, J 13, 6), 1.68
2
1
mixture was stirred rapidly for 4 h, after which H NMR
analysis showed complete conversion. The vessel was vented,
and the solvent was concentrated to approximately 30 mL.
The solution was cooled in an ice bath, and concentrated
hydrochloric acid (6.5 mL) was added. The solution was
evaporated, and acetone (20 mL) was added. The solid was
filtered, washed with acetone (2 × 20 mL), and dried under
(3 H, s), 1.61 (1 H, d, J 16), 1.42 (1 H, br), 1.23 (1 H, dd,
J 13, 9), 0.99 (3 H, s), and 0.88 (3 H, s); GC purity 93.8%;
retention time 12.20 min (Zebron ZB5, 30 m × 0.25 mm,
60 °C for 5 min, ramp to 200 °C at 10 °C/min, hold for 5
min).
Received for review March 20, 2006.
OP060063N
1
vacuum to give the title compound (12.64 g, 78%), H NMR
3
(400 MHz, CD OD) δ 7.45-7.27 (5 H, m), 4.86 (1 H, t, J
(
18) Goering, H. L.; Briody, R. G.; Sandrock. G. J. Am. Chem. Soc. 1970, 92,
(19) Sato, T.; Otera, J.; Nozaki, H. Tetrahedron Lett. 1989, 30, 2959-2962.
(20) Klein, J.; Dunkelblum, E. Tetrahedron 1968, 24, 5701-5710.
7
401-7407.
1058
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Vol. 10, No. 5, 2006 / Organic Process Research & Development