V. T. Myllym aÈ ki et al. / Tetrahedron 57 62001) 4ꢀ29±4ꢀ35
4633
this solution was carefully added diꢀtertꢀbutyldicarbonate
10.07 g, 46.2 mmol, 95 mol %) in CH Cl -7 mL). The
substance was used for subsequent reactions without further
puri®cation.
-
2
2
reaction mixture was allowed to warm up to room temperaꢀ
ture and stirred for 45 minutes. The reaction mixture was
washed with 3£30ml of 2 0% citric acid and once with brine
4.7. *S)-2,2-Dimethyl-4-isopropyl-thiazolidine
hydrochloride salt *9)
-
40mL). The organic layer was evaporated to dryness to
yield pure 5 -9.85 g, 48.5 mmol, quant.) as a yellow, viscous
Thiol hydrochloride salt 8 -915 mg, 5.88 mmol, 100 mol %)
was dissolved in acetone -25 mL) and 2,2ꢀdimethoxyꢀ
propane -10mL) was added. The mixture was re¯uxed for
2
0
oil. R -1:1 MeOH:EtOAc)0.40. [a] 215.2 -c1.0,
f
D
1
MeOH). The H NMR spectrum was identical to literature
data.
2
7
12 hours, with thiazolidine hydrochloride salt 9 gradually
precipitating from the reaction medium. The crude product
was ®ltered and washed several times with acetone to yield
4
3
.4. *S)-1-Thio-acetyl-2-amino-N-*tert-butoxycarbonyl)-
-methyl-butane *6)
9
-802 mg, 4.10 mmol, 70%) as a white solid. mp 220±
2
0
2
238C. R -25% MTBE in hexanes)0.35. [a] 130.8
f
D
Triphenylphosphine -17.69 g, 67.4 mmol, 200 mol %) was
dissolved in THF -100 mL) and the solution was cooled to
0
2
1
-
c1.0, MeOH). H NMR -CD OD) d 1.09 -d, 3H,
3
J6.6 Hz), 1.16 -d, 3H, J6.6 Hz), 1.81 -s, 3H), 1.84 -s,
8C. Diꢀisopropyl azodicarboxylate -14.0mL, 67.4 mmol,
00 mol %) was added and the reaction mixture was stirred
3
H), 2.05 -m, 1H), 3.15 -dd, 1H, J11.5 Hz, 9.2 Hz), 3.57
13
-
-
dd, 1H, J11.5 Hz, 7.3 Hz), 3.83 -m, 1H). C NMR
for 30minutes. A white precipitate formed. BOCꢀ lꢀvalinol
-6.85 g, 33.7 mmol, 100 mol %) and thiolacetic acid
5.0mL, 67.4 mmol, 2 00 mol %) in THF -50mL) was
CD OD) d 20.0, 21.0, 27.6, 29.2, 32.6, 34.3, 69.4, 73.2.
3
5
-
1
HRMS m/z calcd. for C H NS -M) 159.1082, found
8
17
1
1
1
59.1121. Anal. calcd. for C H ClNS C 49.08, H 9.27, Cl
8 18
8.11, N 7.16, S 16.38; found C 49.16, H 9.26, N 7.34, S
6.68.
added dropwise over 15 minutes and the mixture was stirred
for 1 hour at 08C and 4 hours at ambient temperature. The
resulting yellow solution was evaporated to dryness and
dissolved in Et O. The precipitated triphenylphosphine
2
4
.8. *S)-4-Isopropyl-thiazolidine hydrochloride salt *10)
oxide was ®ltered off, and the ®ltrate was evaporated to
dryness. The precipitation procedure was repeated several
times. The crude product was puri®ed by MPLC -12.5%
MTBE in hexanes) to yield 6 -7.13 g, 27.3 mmol, 81%) as
Thiol hydrochloride salt 8 -258 mg, 1.66 mmol, 100 mol %)
was dissolved in ethanol -2.5 mL) and 35% aqueous formꢀ
aldehyde solution -131 mL,1.66 mmol, 100 mol %) was
added. The mixture was stirred at ambient temperature for
30minutes and then at 70 8C for 30minutes. The reaction
mixture was cooled down and evaporated to dryness. The
crude product was washed several times with acetone to
yield 10 -194 mg, 1.16 mmol, 70%) as a white solid. mp
a white solid. mp 59±608C. R -1:1 MeOH:EtOAc)0.40.
f
2
0
1
[
identical to literature data.
a] 171.2 -c1.0, MeOH). The H NMR spectrum was
D
2
7
4.5. *S)-1-Thio-2-amino-N-*tert-butoxycarbonyl)-3-
methyl-butane *7)
2
D
0
1
1
57±1588C. R -50% MTBE in hexanes)0.38. [a]
f
1
22.1 -c1.0, MeOH). H NMR -CD OD) d 1.09 -d, 3H,
3
Thiol acetate 6 -1.50g, 5.74 mmol, 1 00 mol %) and KOH
644 mg, 11.5 mmol, 200 mol %) were dissolved in methaꢀ
J6.6 Hz), 1.15 -d, 3H, J6.6 Hz), 2.07 -m, 1H), 2.99 -dd,
-
1
H, J11.5 Hz, 9.7 Hz), 3.47 -m, 2H), 4.35 -d, 1H,
nol -10mL). The solution was stirred for 30 minutes at
ambient temperature after which the reaction was quickly
quenched with 50% citric acid -25 mL). CH Cl -30mL)
1
3
J10.0 Hz), 4.42 -d, 1H, J10.0 Hz). C NMR -CD OD)
3
d 19.6, 20.3, 31.3, 33.3, 70.7. HRMS m/z calcd. for
C H NS -M) 131.0769, found 131.0755.
2
2
1
6
13
was added and the resulting organic layer was washed
with 20% citric acid -2£20mL) and once with brine
-
-
30mL), dried and evaporated to dryness to yield
7
1.26 g, 5.74 mmol, quant.) as a white solid. mp 48±498C.
4.9. *S)-2,2-Dimethyl-3-tert-butoxycarbonyl-4-isopropyl-
thiazolidine *11)
2
D
0
R -33% MTBE in hexanes)0.38. [a] 12.2 -c1.0,
f
1
MeOH). H NMR -CDCl ) d 0.89 -d, 3H, J6.8 Hz), 0.90
Thiazolidine hydrochloride salt 9 -673 mg, 3.44 mmol,
100 mol %) and diꢀtertꢀbutyldicarbonate -998 mg, 4.57
mmol, 133 mol %) were dissolved in acetonitrile -10mL).
DIPEA -611 ml, 3.51 mmol, 102 mol %) was added dropꢀ
wise to this solution at room temperature. The mixture was
stirred at 508C for 14 days. The reaction mixture was cooled
down and evaporated to dryness. The crude product was
puri®ed by MPLC -14% MTBE in hexanes) to yield 11
3
-
d, 3H, J6.8 Hz), 1.28 -t, 1H, J8.3 Hz), 1.43 -s, 9H), 1.85
app. septet, 1H, J6.8 Hz), 2.66 -dd, 2H, J8.3 Hz,
-
5
1
3
.4 Hz), 3.49 -m, 1H), 4.61 -d, 1H, J7.9 Hz). C NMR
-
HRMS m/z calcd. for C H NO S -MꢀCH ) 204.1058,
CDCl ) d 18.0, 19.4, 27.6, 28.3, 30.2, 57.1, 79.3, 155.7.
3
1
9
18
2
3
found 204.1091.
4.6. *S)-1-Thio-2-amino-3-methyl-butane hydrochloride
salt *8)
-625 mg, 2.41 mmol, 70%) as a colorless liquid. R -25%
f
2
0
MTBE in hexanes)0.61. [a] 143.7 -c0.38, MeOH).
D
1
H NMR --CDCl ) , 508C) d 0.96 -d, 1H, J6.9 Hz), 0.97
2
2
Thiol 7 -1.32 g, 6.02 mmol, 100 mol %) was dissolved in
methanol -10mL) and concentrated HCl -10mL, 37%
aqueous solution) was added. The reaction mixture was
re¯uxed for 8 hours. Evaporation to dryness followed by
evaporation from a suspension with toluene yielded 8
-d, 1H, J6.9 Hz), 1.48 -s, 9H), 1.77 -s, 3H), 1.80-s, 3H),
2.20-app. septet, 1H, J6.9 Hz), 2.69 -dd, 1H, J11.7 Hz,
1.5 Hz), 3.10-dd, 1H, J11.7 Hz, 6.4 Hz), 4.20-app. td,
1
3
1H, J6.4 Hz, 1.5 Hz). C NMR -CDCl ) d 19.4, 19.9,
3
28.4, 29.4, 30.6, 31.6, 69.3, 70.0, 79.8, 153.3. HRMS m/z
calcd. for C H NO S -M1H) 260.1684, found 260.1696.
1
-
915 mg, 5.87 mmol, 98%) as a semiꢀsolid mass. The
1
3
26
2