SYNTHESIS
October 1998
1455
2
3
The 1H and 19F NMR data agree with published values.9
49.6 Hz, =CH(E)], 4.55 dd, 1H, JH,H = 2.6 Hz, JH,F = 17.4 Hz,
=CH(Z)], 7.27–7.34 and 7.59–7.65 (m, 4H, Harom), 8.18 (s, 1H,
2
2
13C NMR: δ = 26.9 (dt, JC,F = 33.2 Hz, CH2Br), 94.3 (dt, JC,F
=
20.3 Hz, =CH2), 161.2 (ds, 1JC,F = 254.3 Hz, CF).
CH=N).
GC/MS: m/z (%) = 140/138 (25) [M+], 59 (100) [M+ – Br].
IR (film): ν = 1670 (s, C=C), 1282 cm–1 (s, C–F).
13C NMR: δ = 22.8 (q, CH3), 28.0 [q, C(CH3)3], 42.1 (dt, JF,C
=
=
2
25.4 Hz, CH2), 67.4 [s, C(CH3)N], 81.6 [s, C(CH3)3], 93.7 (dt, 2JF,C
20.3 Hz, =CH2), 128.6, 128.7, 129.4 and 130.8 (d, CHarom), 134.9 and
1
tert-Butyl 2-(p-Chlorobenzylideneamino)propionate (10):
136.8 (s, Carom), 158.2 (d, CHN), 163.0 (ds, JF,C = 292.5 Hz, CF),
In a modified procedure appearing in ref,21 rac-alanine tert-butyl
ester22 (18.0 g, 124 mmol) and p-chlorobenzaldehyde (10.0 g,
71 mmol) were dissolved in CH2Cl2 (150 mL) and MgSO4 (12.0 g)
was added. The mixture was stirred for two days at r.t. The solution
was filtered and the solvent removed in vacuo. The residue was dis-
solved in Et2O (80 mL) and washed subsequently with water (50 mL)
and sat. aq NaCl (50 mL). The organic layer was dried (MgSO4) and
the solvent evaporated; yield: 15.53 g (83%); mp 42°C (pentane).
171.8 (s, COO).
19F NMR: δ = –86.8 (m).
GC/MS: m/z (%) = 325/327 (10/4) [M+], 183/185 (100/33).
IR (film): ν = 1728 (s, C=O), 1672 (s, C=C), 1643 cm–1 (s, C=N).
Anal. calcd for C17H21ClFNO2 (325.81): C 62.67, H 6.50, N 4.30,
found: C 62.30, H 6.63, N 4.45.
tert-Butyl 2-Amino-4-fluoropent-4-enoate (7):
3
1H NMR: δ = 1.45 [s, 9H, C(CH3)3], 1.47 (d, 3H, JH,H = 6.9 Hz,
Similarly to a known hydrolysis procedure for imines,23 to tert-butyl
2-(diphenylmethyleneamino)-4-fluoropent-4-enoate (6) (1.73 g,
4.9 mmol) in CH2Cl2 (56 mL) and THF (56 mL) were added
CF3COOH (11 mL) and water (14 mL) and the mixture stirred at r.t. for
4 h. Sat. NaHCO3 (20 mL) and then solid NaHCO3 (10 g) were added
to neutralize the solution. The organic layer was separated and the
aqueous layer washed with CH2Cl2 (5 × 15 mL). The combined organic
layers were washed with sat. aq NaCl (20 mL), dried (MgSO4), and the
solvent was evaporated. The crude product was purified by bulb-to-
bulb distillation; yield: 700 mg (76%); bp 40–45°C/15 mbar.
3
CH3), 4.03 (q, 1H, JH,H = 6.9 Hz, CHN), 7.38 and 7.72 (m, 4H,
Harom), 8.24 (s, 1H, HC=N).
13C NMR: δ = 14.1 [q, C(CH3)3], 19.2 (q, CH3), 61.0 [s, C(CH3)3],
128.7 and 129.5 (d, CHarom), 134.1 (q, CCH=N) 136.9 (q, CCl), 161.0
(t, HC=N), 171.6 (q, COO).
GC/MS (Ion Trap): m/z (%) = 267 (8) [M+], 166/168 (100/30) [M+ –
COOC4H9].
IR (KBr): ν = 1729 (s, C=O), 1634 cm–1 (s, C=N).
Anal. calcd for C14H18ClNO2 (267.76): C 62.80, H 6.78, N 5.23,
found: C 62.71, H 6.71, N 5.37.
1H NMR: δ = 1.45 [s, 9H, C(CH3)3], 1.59 (s, 2H, NH2), 2.48 (ddd, 1H,
2JH,H = 14.5 Hz, 3JH,F = 20.5 Hz, 3JH,H = 7.4 Hz, CHH), 2.65 (ddd, 1H,
2JH,H = 14.5 Hz, 3JH,F = 17.6 Hz, 3JH,H = 5.2 Hz, CHH), 3.57 (dd, 1H,
3JH,H = 7.4 Hz, 3JH,H = 5.2 Hz, CHN), 4.36 [dd, 1H, 2JH,H = 2.9 Hz,
Alkylation of Imines; General Procedure:2
To a stirred solution of i-Pr2NH (0.23 mL, 3.0 mmol) in anhyd THF
(7.5 mL) were added at –78°C 1.6 M BuLi in hexane (1.86 mL,
3.0 mmol) and DMPU (0.60 mL, 5 mmol). The cooling bath was re-
moved for 5 min. A solution of the corresponding imino ester
(2.5 mmol), dissolved in anhyd THF (7.5 mL) was added at –78°C.
After 1 h, 3-bromo-2-fluoropropene (4) (417 mg, 3.0 mmol) was in-
jected, and stirring was continued for 2 h at –78°C before the mixture
was allowed to warm up to r.t. overnight. Water (30 mL) was added,
the organic layer separated and the aqueous layer extracted with Et2O
(3 × 10 mL). The combined organic phases were washed with water
(10 mL), sat. aq NaHCO3 (10 mL), sat. aq NaCl (10 mL) and dried
(MgSO4). The solvent was evaporated and the product was filtered
through a short silica gel column (cyclohexane/Et2O 2:1).
3JH,F = 49.4 Hz, =CH(E)], 4.65 [dd, 1H, JH,H = 2.9 Hz, JH,F
=
2
3
17.2 Hz, =CH(Z)].
13C NMR: δ = 27.9 [q, C(CH3)3], 34.6 (dt, 2JC,F = 25.4 Hz, CH2), 52.1
(d, CHN), 81.5 [s, C(CH3)3], 92.9 (dt, 2JC,F = 20.3 Hz, =CH2), 162.8
(ds, 1JC,F = 257.7 Hz, =CF), 173,6 (s, COO).
19F NMR: δ = –95.8 (dddd, 3JH,F = 49.4 Hz, 3JH,F = 20.5 Hz, 3JH,F
17.6 Hz, 3JH,F = 17.2 Hz).
=
GC/MS: m/z (%) = 189 (0.2) [M+], 130 (8) [M+ – C3H4F], 88 (100)
[M+ – COOC4H9].
IR (film): ν = 3387 (m, N–H), 1734 (s, C=O), 1676 cm–1 (s, C=C).
Anal. calcd for C9H16FNO2 (189.23): C 57.13, H 8.52, N 7.40, found:
C 56.83, H 8.64, N 7.21.
tert-Butyl 2-(Diphenylmethyleneamino)-4-fluoropent-4-enoate (6):
From 5 (774 mg, 2.5 mmol) and 4 (417 mg, 3.0 mmol) was obtained
6; yield: 840 mg (95%); mp 66–67°C (pentane).
tert-Butyl 2-Amino-4-fluoro-2-methylpent-4-enoate (12):
tert-Butyl 2-(p-chlorobenzylideneamino)-4-fluoro-2-methylpent-4-
enoate (11) (2.95 g, 10 mmol) was dissolved in Et2O (30 mL) and
1 N HCl (15 mL) was added. The mixture was stirred for 3 h at r.t.
The aqueous layer was separated and the organic layer was extracted
with 1 N HCl (3 × 15 mL). The combined aqueous layers were neu-
tralized with solid K2CO3 (15 g) and extracted with CH2Cl2 (5 × 20
mL). The combined organic phases were washed with sat. aq NaCl
(30 mL) and dried (MgSO4). The solvent was evaporated and the
crude product was purified by bulb-to-bulb distillation; yield: 1.64 g
(73%); bp 45°C/15 mbar.
1H NMR: δ = 1.43 [s, 9H, C(CH3)3], 2.70–2.85 (m, 2H, CH2), 4.18
(dd, 1H, 3JH,H = 4.8 Hz, 3JH,H = 8.3 Hz, CHN), 4.31 [ddd, 1H, 2JH,H
=
2.6 Hz, 3JH,F = 49.8 Hz, 4JH,H = 0.7 Hz, =CH(E)], 4.54 [dd, 1H, 2JH,H
= 2.6 Hz, 3JH,F = 16.9 Hz, =CH(Z)], 7.44–7.16 (m, 10H, Harom).
13C NMR: δ = 28.0 [q, C(CH3)3], 36.2 (dt, 2JC,F = 25.4 Hz, CH2), 81.5
[s, C(CH3)3], 63.0 (d, CHN), 92.3 (dt, 2JC,F = 14.5 Hz, =CH2), 130.2,
128.8, 128.7, 128.6, 128.3, 128.0 and 127.7 (d, C–Harom), 139.6 and
1
136.2 (s, Carom), 163.2 (ds, JC,F = 256.8 Hz, CF), 170.1 (s, C=N),
1H NMR: δ = 1.34 (s, 3H, CH3), 1.47 [s, 9H, C(CH3)3], 1.70 (s, 2H,
NH2), 2.43 (dd, 1H, 2JH,H = 14.6 Hz, 3JH,F = 24.3 Hz, CHH), 2.71 (dd,
171.2 (s, COO).
19F NMR: δ = –95.5 (m).
GC/MS: m/z (%) = 353 (16) [M+], 294 (4) [M+ – C3H4F], 252 (100)
[M+ – C5H9O2], 192 (30) [Ph2C=NC+].
2
3
2
1H, JH,H = 14.6 Hz, JH,F = 17.4 Hz, CHH), 4.35 [dd, 1H JH,H
=
2.9 Hz, 3JH,F = 49.4 Hz, =CH(E)], 4.66 [dd, 1H, 2JH,H = 2.9 Hz, 3JH,F
IR (KBr): ν = 1714 (s, C=O), 1681 (s, C=C), 1624 cm–1 (m, C=N).
Anal. calcd for C22H24FNO2 (353.44): C 74.76, H 6.84, N 3.96,
found: C 74.59, H 6.84, N 4.14.
= 17.2 Hz, =CH(Z)].
2
13C NMR: δ = 26.8 (q, CH3), 27.8 [q, C(CH3)3], 43.2 (dt, JF,C
25.4 Hz, CH2), 56.6 [s, C(CH3)N], 81.3 [s, C(CH3)3], 93.7 (dt, 2JF,C
22.9 Hz, =CH2) 163.1 (ds, 1JF,C = 259 Hz, CF), 175.5 (s, COO).
19F NMR: δ = –92.4 (dddd, 3JF,H = 17.2 Hz, 3JF,H = 17.4 Hz 3JF,H
24.3 Hz, 3JF,H = 49.4 Hz).
=
=
tert-Butyl 2-(p-Chlorobenzylideneamino)-4-fluoro-2-methylpent-
4-enoate (11):
=
From 10 (668 mg, 2.5 mmol) and 4 (417 mg, 3.0 mmol) was obtained
11 as an oil; yield: 750 mg (92%).
GC/MS (Ion Trap): m/z (%) = 202 (5) [M+ – H], 102 (75) [M+ –
COOtBu], 42 (100) [C2H4N+].
1H NMR: δ = 1.39 [s, 9H, C(CH3)3], 1.44 (s, 3H, CH3), 2.6–2.9 (AB,
Anal. calcd for C10H18FNO2 (203.25): C 59.10, H 8.93, N 6.89,
found: C 58.75, H 9.10, N 6.89.
2
2
3
2H, JHH = 14.5 Hz, CH2), 4.36 [dd, 1H, JH,H = 2.6 Hz, JH,F
=