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silica gel (eluent EtOAc/petroleum ether 0.5:9.5) to give 25.2 (c 2, MeOH). Anal. calcd for C12H19NOꢀHCl: C,
0.69 g of a white solid (88% yield): mp 97–988C; [a]2D0
5
62.73; H, 8.77; N, 6.10. Found: C, 62.65; H, 8.76; N, 6.25.
122.0 (c 2, CHCl3); IR (KBr): 1771, 1720 (C¼¼O) cm21; 1H
NMR: d 1.24 (d, J 5 6.0 Hz, 3H, CH3CH), 1.96–2.22 (m
overlapping s at 2.24, 2H, CH2CH), 2.24 (s overlapping m
at 1.9622.22, 6H, CH3Ar), 3.78–4.02 (m, 2H, CH2N), 4.21
(apparent sextet, J 5 6.0 Hz, 1H, CH), 6.8426.92 (m, 1H,
ArO, HC-4), 6.96 (d, J 5 7.4 Hz, 2H, ArO HC-3,5),
7.6827.76 (m, 2H, Ar HC-5,6), 7.8027.88 (m, 2H, Ar HC-
4,7); 13C NMR: d 17.5 (2C), 19.9 (1C), 35.3 (1C), 36.0 (1C),
75.4 (1C), 123.4 (2C), 123.5 (1C), 129.1 (2C), 131.5 (2C),
132.4 (2C), 134.2 (2C), 154.3 (1C), 168.6 (2C); MS (70 eV)
m/z (%) 323 (M1, 1), 160 (100).
(1)-(R )-tert-Butyl (3-hydroxy-1-phenylpropyl)car-
bamate (R )-15. To a solution of (R)-14 (0.42 g, 1.60
mmol) in dry THF (20 ml), LiAlH4 (0.12 g, 3.20 mmol)
was added under N2 atmosphere at 08C and the mixture
stirred for 16 h. The reaction was quenched by the careful
addition of cold water until the end of gas evolution. After
evaporation of the solvent, the residue was taken up with
EtOAc, washed with 2 N NaOH and dried over Na2SO4.
The filtrate was concentrated under vacuum to give 0.35 g
(88%) of a colorless oil: [a]2D0 5 155.5 (c 2.2, CHCl3); IR
1
(neat): 3348 (OH), 1693 (C¼¼O) cm21; H NMR: d 1.44 (s,
9H, t-Bu), 1.74–1.90 (m, 1H, CHHCH), 1.98–2.16 (m, 1H,
CHHCH), 3.18 (br s, 1H, OH), 3.69 (dd, 2H, J 5 7.6, 3.7
Hz, CH2O), 4.80–4.96 (m, 1H, CH), 5.0 (br s, 1H, NH),
7.17 (d, J 5 6.9 Hz, 1H, Ar HC-4), 7.20–7.40 (m, 4H, Ar
HC-2,3,5,6); 13C NMR: d 28.5 (3C), 39.7 (1C), 51.8 (1C),
59.3 (1C), 80.3 (1C), 126.6 (2C), 127.7 (2C), 129.0 (1C),
142.2 (1C), 156.7 (1C); MS (70 eV) m/z (%) 206 (M1 – 45,
(–)-(S )-2-[3-(2,6-Dimethylphenoxy)butyl]-1H-iso-
indole-1,3(2H)-dione (S )-13. Prepared as reported
above for (R)-13 starting from (S)-12. White solid (60%
yield): mp 95–978C; [a]2D0 5 221.0 (c 1.1, CHCl3). Spectro-
metric data were in agreement with those reported for the
(R)-isomer.
(1)-(S)-3-(2,6-Dimethylphenoxy)butan-1-amine (S)-3. 33), 150 (100).
Prepared as reported above for (R)-2 starting from (S)-13.
(–)-(S )-tert-Butyl (3-hydroxy-1-phenylpropyl)carba-
mate (S )-15. Prepared as reported above for (R)-15
Slightly yellowish oil (72% yield); [a]2D0 5 10.4 (c 2,
CHCl3). IR (neat): 3367 (NH2) cm21 1H NMR: d 1.18
;
starting from (S)-14. Colorless oil (73% yield); [a]2D0
5
(d overlapping br s at 1.25, J 5 6.3 Hz, 3H, CH3CH), 1.25
(br s overlapping d at 1.18, 2H, NH2), 1.78 (apparent dq,
six lines, J 5 15.5, 6.9 Hz, 1H, CHHCH), 1.92 (apparent
dq, six lines, J 5 13.5, 6.9 Hz, 1H, CHHCH), 2.26 (s, 6H,
CH3Ar), 2.90 (apparent br s, 2H, CH2), 4.20 (apparent sex-
tet, J 5 6.2 Hz, 1H, CH), 6.8526.95 (m, Ar HC-4), 6.99
(d, J 5 7.2 Hz, 2H, Ar HC-3,5); 13C NMR: d 17.5 (2C), 20.1
(1C), 39.2 (1C), 41.1 (1C), 76.1 (1C), 123.4 (1C), 129.1
(2C), 131.5 (2C), 154.4 (1C); MS (70 eV) m/z (%) 193
(M1, 6), 122 (100).
259.2 (c 2.2, CHCl3). 1H NMR data were in agreement
with those reported for the (R)-isomer.
(1)-(R )-tert-Butyl [3-(2,6-dimethylphenoxy)-1-phe-
nylpropyl]carbamate (R )-16. Prepared as reported
above for (R)-10 starting from (R)-15. White solid (79%
yield): mp 962978C; [a]2D0 5 125.3 (c 2, CHCl3); IR (KBr):
1
3370 (NH), 1683 (C¼¼O) cm21; H NMR: d 1.42 (s, 9H, t-
Bu), 2.24 (s overlapping m at 2.16–2.36, 6H, CH3Ar), 2.16–
2.36 (m overlapping s at 2.24, 2H, CH2CH), 3.70–3.85 (m,
2H, CH2O), 4.95 (br s, 1H, CH), 5.43 (br s, 1H, NH),
6.8526.95 (m, 1H, ArO HC-4), 6.99 (d, J 5 7.1 Hz, 2H,
ArO HC-3,5), 7.25–7.35 (m, 1H, Ar HC-4), 7.35 (m, 4H, Ar
HC-2,3,5,6); 13C NMR: d 16.6 (2C), 28.6 (3C), 37.3 (1C),
53.2 (1C), 69.3 (1C), 79.6 (1C), 124.1 (2C), 126.4 (1C),
127.4 (2C), 128.8 (2C), 129.0 (1C), 131.1 (2C), 142.8 (1C),
155.5 (1C), 156.0 (1C); MS (70 eV) m/z (%) 281 (M1 – 74,
6), 178 (100).
(1)-(S)-3-(2,6-Dimethylphenoxy)butan-1-amine hydro-
chloride (S)-3ꢀHCl. Prepared as reported above for (R)-
2ꢀHCl starting from (S)-3. White solid (53% yield): mp
117–118 8C (abs EtOH/Et2O); 98% ee (1H NMR); [a]2D0
5
15.7 (c 2, MeOH); IR (KBr): 2970 (NH31) cm21; H NMR
(CD3OD, d 3.11): d 0.97 (d, 3H, J 5 6.0 Hz, CH3CH), 1.80–
1.95 (m, 2H, CH2CH), 2.06 (s, 6H, CH3Ar), 2.92–3.08 (m,
2H, CH2N), 4.15 (apparent sextet, J 5 6.0 Hz, 1H, CH),
6.6626.74 (m, 1H, Ar HC-4), 6.80 (d, J 5 7.4 Hz, 2H, Ar
1
(–)-(S)-tert-Butyl [3-(2,6-dimethylphenoxy)-1-phenyl-
HC-3,5); 13C NMR (CD3OD, d 47.7): d 16.2 (2C), 18.3 propyl]carbamate (S)-16. Prepared as reported above
(1C), 34.5 (1C), 36.9 (1C), 75.0 (1C), 123.5 (1C), 128.8 for (R)-10 starting from (S)-15. White solid (72% yield):
(2C), 131.0 (2C), 153.4 (1C). Anal. calcd for mp 962978C; [a]2D0 5 225.9 (c 1.9, CHCl3). Spectroscopic
C12H19NOꢀHCl: C, 62.73; H, 8.77; N, 6.10. Found: C, 62.67; data were in agreement with those reported for the (R)-
H, 8.63; N, 6.16.
isomer.
(–)-(R)-3-(2,6-dimethylphenoxy)-1-phenylprpan-1-amine
(–)-(R)-3-(2,6-Dimethylphenoxy)butan-1-amine (R)-3.
Prepared as reported above for (R)-2 starting from (R)-13.
Slightly yellowish oil (78% yield); [a]2D0 5 20.4 (c 2,
CHCl3). Spectrometric data were in agreement with those
reported for the (S)-isomer.
hydrochloride (R)-5ꢀHCl. To a solution of (R)-16 (0.21
g, 0.6 mmol) in 5 ml of EtOAc, 3 N HCl (3 ml) was added
at 08C. The reaction mixture was stirred at room tempera-
ture for 15 h. The solvent was evaporated under reduced
pressure azeotropically removing water. Crystallization
(–)-(R)-3-(2,6-Dimethylphenoxy)butan-1-amine hydro- from abs EtOH/Et2O gave 0.11 g (65% yield) of (R)-5ꢀHCl
chloride (R)-3ꢀHCl. Prepared as reported above for (R)- as white crystals: mp 185–1868C; ꢁ99% ee (CE) (injection:
2ꢀHCl starting from (R)-3. White solid (60% yield): mp 15 psi/s; BGE: phosphate buffer 0.035 M at pH 5 4.3;
117–1188C (abs EtOH/Et2O); 98% ee (1H NMR); [a]2D0
5
chiral selector: 2-hydroxypropyl-b-cyclodextrin 40 mg/ml;
Chirality DOI 10.1002/chir