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M. Dıaz-Gavilan et al. / Tetrahedron 60 (2004) 11547–11557
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vacuum. Purification by flash chromatography with gradient
elution using mixtures EtOAc/hexane (1/20/1/5), afforded
the final amide 9d as a colourless liquid (69% yield). In
CDCl3 at rt two isomers are observed: isomer A (60%)
(numbers without primes), isomer B (40%) (numbers with
4.1.18. (RS)-1-Benzoyl-3-methoxy-1,2,3,5-tetrahydro-
4,1-benzoxazepine (9f). A solution of 9c (1 equiv) in
dried CH2Cl2 (3 mL/mmol 9c) was prepared under argon
and cooled to 0 8C. At this temperature, TEA (3 equiv) and
then benzoyl chloride (2 equiv) were added dropwise. The
mixture was stirred between 0 and 5 8C for 3 h and
afterwards diluted with CH2Cl2. The organic layer was
washed with water, dried (Na2SO4) and concentrated under
vacuum. The final product carrying the benzoyl moiety was
purified by flash chromatography (gradient elution mixtures
EtOAc/hexane 1/20/1/4) as a white solid, mp 104.5–
105.0 8C (quantitative yield). CDCl3, rt: Isomer A (86%)
(numbers without primes), isomer B (14%) (numbers with
1
primes): H NMR (CDCl3, 300 MHz): d (ppm) 7.39–7.10
(m, 4H, 4H0), 5.15 (d, JgemZ13.0 Hz, 1H0), 5.05 (d, Jgem
Z
14.0 Hz, 1H0), 4.82 (d, Jgem 2–2Z13.6 Hz, 1H, H2), 4.76–
4.67 (m, 2H, 1H0), 4.49 (d, Jgem 5–5Z14.1 Hz, 1H, H5), 4.15
(d, JgemZ13.0 Hz, 1H0), 3.49 (s, 3H, OCH3), 3.43 (s, 3H,
OCH03), 2.85 (d, JgemZ14.0 Hz, 1H0), 2.70 (dd, J3–2
Z
8.8 Hz, 1H, H2), 2.26 (m, 2H, COCH2, COCH02), 2.06 (m,
2H, COCH2, COCH02), 1.58 (m, 4H, CH3CH2, CH3CH002),
1
primes): H NMR (CDCl3, 300 MHz): d (ppm) 8.10 (d,
0
0
0.83 (t, JCH2–CH3ZJCH2 –CH3 Z7.4 Hz, 6H, CH3, CH 3).
2H0), 7.59 (t, 1H0), 7.47 (t, 2H0), 7.38–7.04 (m, 7H, 4H00),
6.93 (t, 1H), 6.61 (d, 1H), 5.39–5.06 (bs), 4.87 (bs, 1H, 1H ),
4.70–4.33 (bs), 3.51 (s, 6H, OCH3, OCH03). 13C NMR
(CDCl3, 100 MHz): d (ppm) 170.11 (CO), 135.59, 133.55,
130.18, 130.01, 129.17, 128.65, 128.49, 128.07, 127.86,
126.68, 126.34 (Caromatic), 101.54 (C3), 64.60 (C5), 55.74
(OCH3), 50.47 (C2). DMSO-d6, 808C: Isomer A (90%)
(numbers without primes), isomer B (10%) (numbers with
primes): 1H NMR (DMSO-d6, 400 MHz): d (ppm) 7.91 (m,
2H0), 7.56 (dddd, J1ZJ2Z7.4 Hz, J3ZJ4Z1.4 Hz, 1H0),
7.45–7.38 (m, 3H0), 7.32 (dd, JZ7.5, 1.4 Hz, 2H), 7.30–
7.17 (m, 4H, 3H0), 7.09 (ddd, J1ZJ2Z7.5 Hz, J3Z1.2 Hz,
1H), 6.97 (ddd, J1ZJ2Z7.6 Hz, J3Z1.5 Hz, 1H), 6.69 (d,
13C NMR (CDCl3, 75 MHz): d (ppm) 173.01 (CO), 143.60,
0
0
142.00, 136.70, 136.27 (C9a , C9a, C5a , C5a), 129.81–127.24
0
0
0
0
0
(C6, C6 , C7, C7 , C8, C8 , C9, C9 ), 102.67 (C3), 99.03 (C30 ),
0
66.05 (C5), 61.58 (C5 ), 56.28 (OCH3), 55.09 (OCH 3),
50.71 (C2), 48.94 (C2 ), 36.07 (COCH2, COCH 2), 19.83
0
0
(CH3CH2, CH3CH02), 13.85 (CH3, CH03). LSIMS m/z
(relative intensity) 274 (13), 273 (17), 272 [(MCNa)C,
66], 266 (16), 265 (50), 264 (25), 263 (34), 260 (19), 251
(11), 250 [(MCH)C, 47], 249 (20), 248 (23), 247 (30), 246
(14), 245 (9), 244 (17), 243 (27), 237 (42), 236 (19), 235
(21), 234 (15), 233 (29), 232 (18), 231 (35), 230 (21), 229
(30), 228 (17), 227 (38), 226 (16), 225 (8), 222 (37), 221
(100), 220 (27), 219 (49), 218 (53). HR LSIMS m/z calcd for
C14H19NO3Na (MCNa)C: 272.1263, found: 272.1260.
Anal. for C14H19NO3: calcd C 67.45; H 7.68; N 5.62.
Found: C 67.56; H 7.43; N 5.60.
0
JZ7.6 Hz, 1H), 5.07 (d, JgemZ13.9 Hz, 2H, H5,5 ), 4.77
0
(dd, JZ5.0, 2.9 Hz, 2H, H3,3 ), 4.56 (d, JgemZ13.9 Hz, 2H,
0
0
H5,5 ), 3.90 (bs), 3.40 (s, 6H, OCH3, OCH 3), 3.29 (m).
LSIMS m/z (relative intensity) 285 (15), 284 [(MCH)C,
100], 283 (MC, 30), 282 (12). HR LSIMS m/z calcd for
C17H18NO3 (MCH)C: 284.1287, found: 284.1282. Anal.
for C17H17NO3: calcd C 72.07; H 6.05; N 4.94. Found: C
71.92; H 6.00; N 4.99.
4.1.17. (RS)-3-Methoxy-1-trifluoroacetyl-1,2,3,5-tetrahy-
dro-4,1-benzoxazepine (9e). Reaction of 9c with TFAA
according to the procedure described for the preparation of
9d. After 18 h stirring at rt, the reaction mixture was diluted
with CH2Cl2 and the organic layer washed with water, dried
(Na2SO4) and concentrated under vacuum. Purification was
performed by flash chromatography (gradient elution
mixtures EtOAc/hexane 1/50/1/16), to yield the final
product 9e as a white solid, mp 76.0–77.0 8C (79% yield). In
CDCl3 at rt two isomers are observed: isomer A (45%)
(numbers without primes), isomer B (55%) (numbers with
4.1.19. N-[2-(tert-Butyldimethylsilanyloxymethyl)phe-
nyl]-N-isopropyl-4-nitrobenzenesulfonamide (20). Com-
pound 20 was obtained from 15b with the same procedure
described for the preparation of 16b, but using an excess of
hydroxyacetaldehyde dimethyl acetal (4.3 equiv). Flash
chromatography purification with a gradient elution mixture
EtOAc/hexane (1/50/1/20) afforded 20 (38% yield) as a
white solid (mp 178.0–179.0 8C) and 16b (31% yield).
1
primes): H NMR (CDCl3, 300 MHz): d (ppm) 7.39–7.18
(m, 4H0, 4H), 5.21 (d, Jgem 5 –5 Z13.2 Hz, 1H, H5 ), 4.91
1
0
0
0
Compound 20: H NMR (CDCl3, 300 MHz): d (ppm) 8.33
(d,
0
0
0
0
0
(dd, Jgem 2 –2 Z13.8 Hz, J3 –2 Z1.4 Hz, 1H, H2 ), 4.75–4.68
J6–5 sulfonamideZJ3–2 sulfonamide
8.8 Hz,
2H,
(m, 1H0, 3H), 4.56 (d, Jgem 5–5Z14.0 Hz, 1H, H5), 4.18 (d,
0
1H, H5 ), 3.51 (s, 3H, OCH3), 3.44 (s, 3H, OCH 3), 3.06 (d,
H3,5 sulfonamide), 7.89 (d, 2H, H2,6 sulfonamide), 7.73 (d, JZ
7.2 Hz, 1H), 7.44 (ddd, J1ZJ2Z7.6 Hz, J3Z0.8 Hz, 1H),
7.16 (ddd, J1ZJ2Z7.7 Hz, J3Z1.5 Hz, 1H), 6.58 (dd, JZ
7.9, 0.8 Hz, 1H), 4.90 (d, Jgem CH2Z15.0 Hz, 1H, CH2),
4.85 (d, 1H, CH2), 4.61 [m, 1H, CH(CH3)2], 1.13 [d, JCH–
CH3Z6.7 Hz, 3H, CH(CH3)2], 1.00 [d, JCH–CH3Z6.8 Hz,
3H, CH(CH3)2], 0.96 [s, 9H, (CH3)3C], 0.14 [2s, 6H,
(CH3)2Si]. LSIMS m/z (relative intensity) 490 (4), 489 (15),
488 (36), 487 [(MCNa)C, 100], 468 (1), 467 (5), 466 (12),
465 [MCH)C, 39], 410 (3), 409 (11), 408 (25), 407 (87),
393 (2), 392 (3), 391 (7), 336 (1), 335 (5), 334 (13), 333
(65), 331 (2), 330 (3), 329 (15), 282 (1), 281 (2), 280 (4),
279 (18). HR LSIMS m/z calcd for C22H32N2O5SSiNa (MC
Na)C: 487.1699, found: 487.1702.
0
0
1H, H2 ), 2.85 (dd, Jgem 2–2Z13.0 Hz, J3–2Z8.2 Hz, 1H,
H2). 13C NMR (CDCl3, 100 MHz): d (ppm) 156.74 (q, JCO–
FZ36.0 Hz, CO), 156.65 (q, JCO –FZ36.0 Hz, CO0), 140.40
0
0
(C9a ), 138.85 (C9a), 136.55 (C5a ), 136.42 (C5a), 129.77–
0
0
0
0
0
0
126.75 (C6 , C6, C7 , C7, C8 , C8, C9 , C9), 116.44 (q, JC –F
Z
287.0 Hz, CF03), 116.25 (q, JC–FZ287.0 Hz, CF3), 102.24
0
(C3), 98.56 (C3 ), 66.32 (C5), 61.30 (C5 ), 56.44 (OCH3),
0
55.24 (OCH 3), 52.90 (C2), 51.27 (C2 ). LSIMS m/z (relative
0
0
intensity) 331 (7), 330 (26), 329 (100), 308 (8), 307 (35),
299 (12), 299 (12), 298 [(MCNa)C, 51], 289 (21), 277 (9),
276 [(MCH)C, 34], 274 (15), 273 (15), 259 (13), 257 (11),
245 (22), 244 (61), 243 (13), 239 (9), 217 (14), 216 (18), 215
(29). HR LSIMS m/z calcd for C12H12NO3F3Na (MCNa)C:
298.0670, found: 298.0673. Anal. for C12H12FNO3: calcd C
52.37; H 4.39; N 5.09. Found: C 52.41; H 4.22; N 5.21.
4.1.20. 2-(2,2-Dimethoxyethylaminomethyl)phenol (21).
A solution of 2-hydroxybenzaldehyde (1 equiv) in EtOH