Trialkylamines More Planar Than Triisopropylamine
These electrodes were repolished with 0.3 µm alumina powder
between experiments.
85.429(4)°, γ ) 83.200(4)°. A total of 10 352 reflections (4555
independent) were collected to a maximum 2θ of 50.36°, data-
to-parameter ratio 16.7. Structure solution and refinement on F2
resulted in final R indices of R1 ) 0.0515, wR2 ) 0.1388 (F2 >
2σ(F2)), R1 ) 0.0665, wR2 ) 0.1477 (all data) and a goodness
of fit on F2 of 1.057.
General Procedure for the Diester Reductions. Under a
nitrogen atmosphere, the diester (1 equiv, 0.7-1.8 mmol) in 3
mL of dry THF was added dropwise to a stirred suspension of
lithium aluminum hydride (6 equiv, n grams) in 7 mL of dry
THF. The reaction was heated to 60 °C for 12 h or 2 days, as
indicated below. The reaction mixture was cooled, and to it were
added sequentially n mL of water, n mL of 5% aqueous NaOH,
and 3n mL of water. The mixture was filtered, and the filtrate
was evaporated. The residue was purified by recrystallization
or column chromatography as specified in each case. This
procedure was also followed in the reduction of ester-amide 4.
2-(Dicyclohexylamino)propane-1,3-diol, 7. Diester 2 (230 mg,
0.74 mmol), LiAlH4 (170 mg, 4.47 mmol), 12 h, recrystallization
from EtOAc/hexane 2:1 (v/v). Colorless solid, mp 135-135.5
°C, 180 mg, 95% yield. Anal. Calcd for C15H29NO2: C, 70.54;
H, 11.44; N, 5.48. Found: C, 70.30; H, 11.50; N, 5.51. 1H NMR
(250 MHz, CDCl3): 3.58 (m, 4H), 3.08 (quintet, J ) 7.3 Hz,
1H), 2.60 (m, 2H), 2.43 (br, 2H), 1.79-0.99 (m, 20H). 13C NMR
(63 MHz, CDCl3): 61.9, 58.0, 54.1, 34.4, 26.5, 25.6. A needle-
shaped crystal (1.00 × 0.086 × 0.050 mm) was chosen for X-ray
crystallography. Crystal data: monoclinic, P21/c, Z ) 8, a )
12.9231(11) Å, b ) 6.6306(6) Å, c ) 35.487(3) Å, ꢀ )
96.199(2)°. A total of 29 956 reflections (7517 independent
reflections) were collected to a maximum 2θ of 56.60°, data-
to-parameter ratio 23.1. Structure solution and refinement on F2
resulted in final R indices of R1 ) 0.0608, wR2 ) 0.1276 (F2 >
2σ(F2)), R1 ) 0.1200, wR2 ) 0.1494 (all data) and a goodness
of fit on F2 of 0.921.
2,3-Bis(diisopropylamino)-1-propanol, 11. Ester-amide 4 (320
mg, 1.07 mmol) LiAlH4 (200 mg, 5.26 mmol), 2 days, column
chromatography (CH2Cl2/CH3OH 6:1 (v/v)). Colorless solid, mp
35-35.5 °C, 250 mg, 91% yield. Anal. Calcd for C15H34N2O:
C, 69.71; H, 13.26; N, 10.84. Found: C, 69.63; H, 13.34; N,
1
10.79. H NMR (250 MHz, CDCl3): 3.84 (q, J ) 9.3 Hz, 1H),
3.53 (m, 1H), 3.10 (m, 5H), 2.62 (m, 2H), 1.09 (d, J ) 6.6 Hz,
6H), 1.03 (d, J ) 6.8 Hz, 12H), 0.98 (d, J ) 6.6 Hz, 6H). 13C
NMR (63 MHz, CDCl3): 66.8, 51.5, 49.2, 48.0, 45.1, 23.6, 23.3,
22.5, 18.3. A needle-shaped crystal of 11 (0.50 × 0.02 × 0.02
mm) was selected for X-ray crystallography. Crystal data:
monoclinic P21/n, Z ) 4, a ) 10.9485(6) Å, b ) 11.1399(6) Å,
c ) 14.3517(8) Å, ꢀ ) 103.7000(10)°. A total of 14 117
reflections (3232 independent) were collected to a maximum 2θ
of 51.36°, data-to-parameter ratio 16.5. Structure solution and
refinement on F2 resulted in final R indices of R1 ) 0.0729,
wR2 ) 0.1996 (F2 > 2σ(F2)), R1 ) 0.0945 wR2 ) 0.2191 (all
data) and a goodness of fit on F2 of 1.055.
2-(Dicyclohexylamino)-2-methylpropane-1,3-diol, 14. Diester
12 (420 mg, 1.29 mmol), LiAlH4 (230 mg, 6.05 mmol), 60 °C for 2
days, column chromatography (CH2Cl2/CH3OH 6:1 (v/v)). Colorless
solid, mp 115-116 °C, 230 mg, 66.2% yield. Anal. Calcd for
C16H31NO2: C, 71.33; H, 11.60; N, 5.20. Found: C, 71.59; H, 11.85;
1
N, 5.22. H NMR (250 MHz, CDCl3): 3.54 (q, J ) 10.9 Hz, 4H),
2.86 (br, 2H), 2.74 (m, 2H), 1.79-0.97 (m, 20H), 1.17 (s, 3H). 13C
NMR (63 MHz, CDCl3): 66.6, 64.2, 57.2, 36.1, 27.6, 26.2, 20.4. A
needle-shaped crystal of 14 (1.35 × 0.110 × 0.094 mm) was selected
for X-ray crystallography. Crystal data: monoclinic, P21/c, Z ) 4, a
) 6.4556(7) Å, b ) 13.4106(15) Å, c ) 17.6286(19) Å, ꢀ )
95.762(2)°. A total of 12 299 reflections (2775 independent) were
collected to a maximum 2θ of 50.68°, data-to-parameter ratio 16.0.
Structure solution and refinement on F2 resulted in final R indices of
R1 ) 0.0458, wR2 ) 0.1260 (F2 > 2σ(F2)), R1 ) 0.0511 wR2 )
0.1298 (all data) and a goodness of fit on F2 of 1.052.
2-(Diisopropylamino)propane-1,3-diol, 8. Diester 3 (430 mg,
1.87 mmol), LiAlH4 (360 mg, 9.47 mmol), 12 h, recrystallization
from EtOAc/hexane 1:5 (v/v). Colorless solid, mp 67-68 °C,
300 mg, 92% yield. Anal. Calcd for C9H21NO2: C, 61.68; H,
1
12.08; N, 7.99. Found: C, 61.94; H, 12.18; N, 7.98. H NMR
(250 MHz, CDCl3): 3.60 (m, 4H), 3.16 (septet, J ) 6.5 Hz, 2H),
3.06 (quintet, J ) 7.3 Hz, 1H), 2.68 (br, 2H), 1.07 (d, J ) 6.5
Hz, 12H). 13C NMR (63 MHz, CDCl3): 61.9, 57.0, 44.8, 23.4.
A prism-shaped crystal of 8 (0.50 × 0.30 × 0.30 mm) was
j
chosen for X-ray crystallography. Crystal data: triclinic, P1, Z
2-(Diisopropylamino)-2-methylpropane-1,3-diol, 15. Diester 13
(210 mg, 0.86 mmol) LiAlH4 (170 mg, 4.86 mmol), 12 h, column
chromatography (CH2Cl2/CH3OH 8:1 (v/v)). Pale yellow oil, 120
) 2, a ) 7.4601(7) Å, b ) 7.5153(7) Å, c ) 11.1194(10) Å, R
) 86.462(2)°, ꢀ ) 72.485(2)°, γ ) 64.2070(10)°. A total of
4426 reflections (2239 unique) were collected to a maximum
2θ of 53.46°, data-to-parameter ratio 20.5. Structure solution
and refinement on F2 resulted in final R indices of R1 ) 0.0481,
wR2 ) 0.1241 (F2 > 2σ(F2)), R1 ) 0.0529, wR2 ) 0.1284 (all
data) and a goodness of fit on F2 of 1.034.
1
mg, 72% yield. H NMR (250 MHz, CDCl3): 3.53 (q, J ) 10.6
Hz, 4H), 3.30 (septet, J ) 6.9 Hz, 2H), 3.12 (br, 2H), 1.20 (d,
J ) 6.9 Hz, 6H), 1.19 (s, 3H). 13C NMR (63 MHz, CDCl3):
65.7, 64.7, 46.3, 24.6, 19.4. HRMS Calcd for C10H24NO2 (M +
H) 190.18058; found, 190.18070.
2-(N-tert-butyl-N-isopropylamino)propane-1,3-diol, 9. Diester
5 (350 mg, 1.43 mmol) LiAlH4 (440 mg, 9.47 mmol), 2 days,
column chromatography (CH2Cl2/CH3OH 6:1 (v/v)). Pale yellow
General Procedure for Methylations. A greater than 3-fold
excess (relative to the diester) of NaH as a 50% dispersion in
mineral oil was added to dry THF and filtered under nitrogen,
and the solid transferred quickly to the tared reaction vessel and
weighed. Dry THF (10 mL) was added, followed by the diester,
and the mixture was stirred for 0.5 h. Iodomethane (0.85-0.93
equiv relative to NaH) was added dropwise. The mixture was
stirred at rt until 1H NMR analysis indicated no starting material
remained. TLC was not useful for monitoring the progress of
the reaction since the Rf of the product and the Rf of the starting
material were usually nearly identical. The reaction was
quenched by addition of water and extracted with CH2Cl2. The
combined organic phase was dried over Na2SO4 and filtered,
and the solvent was removed on the rotary evaporator. The
residue was subjected to silica gel column chromatography.
1
oil, 80 mg, 30% yield. H NMR (250 MHz, CDCl3): 3.81-3.64
(AB quartet, 4H), 3.40 (septet, J ) 6.8 Hz, 1H), 3.24 (quintet,
J ) 7.6, Hz, 1H), 1.22 (s, 9H), 1.17 (d, J ) 6.8 Hz, 6H). 13C
NMR (63 MHz, CDCl3): 66.2, 58.8, 57.0, 47.7, 30.9, 24.0.
HRMS calcd for C10H24NO2 (M + H) 190.1807; found,
190.1809.
2-(2,2,6,6-Tetramethyl-1-piperidinyl)propane-1,3-diol, 10. Di-
ester 6 (320 mg, 1.18 mmol) LiAlH4 (260 mg, 6.84 mmol), 2
days, column chromatography (CH2Cl2/CH3OH 6:1 (v/v)).
Colorless solid, mp 105-7 °C, 100 mg, 39% yield. Anal. Calcd
for C12H25NO2: C, 66.93; H, 11.70; N, 6.50. Found: C, 66.78;
1
H, 11.82; N, 6.32. H NMR (250 MHz, CDCl3): 3.80-3.67 (m,
4H), 3.57 (m, 1H), 3.57 (br, 2H), 1.61-1.51 (m, 6H), 1.22 (s,
12H). 13C NMR (100 MHz, CDCl3): 63.5, 58.6, 56.3 (br), 44.8
(br), 30.0, 17.9. 13C NMR (100 MHz, DMSO-d6): 63.3, 59.5,
55.5, 53.9, 44.8, 41.8, 29.8, 17.5. A prism-shaped crystal of 10
(0.550 × 0.160 × 0.128 mm) was selected for X-ray crystal-
Dimethyl 2-(Dicyclohexylamino)-2-methylpropane-1,3-dio-
ate, 12. Diester 2 (310 mg, 1.00 mmol), NaH (110 mg, 4.58
mmol), CH3I (550 mg, 3.87 mmol). Elution solvent EtOAc/
hexane 1:20 (v/v). Afforded 240 mg (74% yield) of 12, as a
1
j
lography. Crystal data: triclinic, P1, Z ) 4, a ) 7.2537(15) Å,
colorless oil. H NMR (250 MHz, CDCl3): 3.73 (s, 6H), 2.67
b ) 12.906(3) Å, c ) 14.907(3) Å, R ) 65.765(4)°, ꢀ )
(m, 2H), 1.83-0.99 (m, 20H), 1.70 (s, 3H). 13C NMR (63 MHz,
J. Org. Chem. Vol. 74, No. 7, 2009 2677