1
0
R. B. REDDY ET AL.
ꢁ
1
1
ꢀ
(
C–H), 1116 (C–O), 691 (¼C–H) cm . H NMR (400 MHz, CDCl , 25 C):
3
d ¼ 7.70–7.62 (m, 4H), 7.44–7.34 (m, 6H), 4.65 (AB system, J ¼ 7.8 Hz, 2H), 4.41 (d,
AB
J ¼ 8.8 Hz, 1H), 3.77–3.69 (m, 1H), 3.67–3.55 (m, 3H), 3.30 (s, 3H), 1.81–1.68 (m, 1H),
13
1
.66–1.48 (m, 2H), 1.44 (s, 9H), 1.06 (s, 9H), 0.87 (s, 6H) ppm. C NMR (100 MHz,
ꢀ
CDCl , 25 C): d ¼ 155.8, 135.7, 133.5, 129.7, 127.7, 97.2, 78.8, 76.1, 66.5, 55.7, 52.2,
3
þ
3
4.9, 32.7, 28.4, 26.9, 19.3, 18.8, 17.9 ppm. HRMS (ESI) m/z [M þ Na] calcd. for
C H NO SiNa 552.3116, found 552.3122.
3
0
47
5
1
1
2b (minor diastereoisomer) TLC: Rf 0.25 (90:10, hexane/EtOAc); H NMR
ꢀ
(
400 MHz, CDCl , 25 C): d ¼ 7.64–7.57 (m, 4H), 7.44–7.34 (m, 6H), 4.57 (d,
3
J ¼ 6.68 Hz, 1H), 4.65 (AB system, J ¼ 6.60 Hz, 2H), 3.71–3.63 (m, 1H), 3.63–3.55 (m,
AB
2
9
H), 3.54–3.48 (m, 1H), 3.22 (s, 3H), 1.84–1.73 (m, 2H), 1.49–1.38 (m, 1H), 1.34 (s,
H), 0.98 (s, 9H), 0.82 (d, J ¼ 6.76 Hz, 3H), 0.78 (d, J ¼ 6.76 Hz, 3H).
Synthesis of ethyl-2-((5R,7R)-7-isopropyl-11,11-dimethyl-9-oxo-2,4,10-trioxa-8-
azadodecan-5-yl)thiazole-4-carboxylate (1)
Lawesson’s reagent (66.2 mg, 0.17 mmol) was added to a solution of N-Boc-c-aminocar-
boxamide 14 (50 mg, 0.17 mmol) in dry THF (5 mL) in a round bottom flask (50 mL) at
room temperature. The resulting solution was further stirred for 12 h at the same tem-
perature under nitrogen atmosphere. After the complete consumption of 14, the reac-
tion mixture was quenched by addition of saturated aq. NaHCO (20 mL) at room
3
temperature and the aqueous layer was extracted with EtOAc (3 ꢂ 30 mL). The com-
bined organic layers was dried over anhydrous Na SO , filtered and concentrated under
2
4
reduced pressure. The crude residue was purified over silica gel column chromatog-
raphy using 80:20 hexane/EtOAc mixture as eluent to afford thioamide 15 (32 mg, 60%)
as a light-yellow liquid and used immediately for thiazole ring formation in the next
step. TLC: Rf 0.53 (30:70, hexane/EtOAc). A round-bottom flask (25 mL) was charged
with activated 3 Å molecular sieves (100 mg), magnetic bead and dry EtOH (5 mL)
under an inert atmosphere. N-Boc-c-aminothioamide 15 (18 mg, 0.07 mmol) and ethyl
bromopyruvate (0.02 mL, 0.10 mmol) was added to the reaction mixture at room tem-
ꢀ
perature. The reaction mixture was heated at 65 C for 1 h. After the consumption of
thioamide 15, as confirmed by TLC, molecular sieves were filtered through Buchner
funnel, solvent evaporated under reduced pressure and the crude residue was purified
over silica gel column chromatography (70:30 hexane/EtOAc) to afford 2-alkyl substi-
tuted thiazole ethyl ester 1 (25 mg, 83%) as colorless liquid. TLC: Rf 0.38 (70:30, hex-
ane/EtOAc). IR (CH Cl ): 2968, 2927 (C–H), 1781, 1745 (C¼O), 1632 (C ¼ N), 1474,
2
2
1
1
366 (C–H), 1172 (C–O), 1162 (S–O), 1029 (C–O), 860 (¼C–H), 701 (C–H) cm-1. H
ꢀ
NMR (400 MHz, CDCl , 25 C): d ¼ 8.12 (s, 1H), 5.09 (br d, J ¼ 7.2 Hz, 1H), 4.71 (d,
3
J ¼ 6.8 Hz, 1H), 4.69 (d, J ¼ 6.8 Hz, 1H), 4.42 (br d, J ¼ 6.8 Hz, 1H), 4.31 (q, J ¼ 6.8 Hz,
2
9
H), 3.76–3.69 (m, 1H), 3.40 (s, 3H), 1.93–1.80 (m, 1H), 1.65–1.56 (m, 2H), 1.36 (s,
13
H), 1.25 (t, J ¼ 6.8 Hz, 3H), 0.89 (d, J ¼ 7.1 Hz, 3H), 0.87 (d, J ¼ 7.1 Hz, 3H) ppm.
C
ꢀ
NMR (100 MHz, CDCl , 25 C): d ¼ 174.7, 161.4, 155.2, 147.1, 127.6, 95.8, 61.4, 56.3,
3
þ
5
1.9, 38.1, 31.7, 29.5, 28.3, 18.7, 17.2, 14.3 ppm. HRMS (ESI) m/z [M þ Na] calcd. for
C H N O SNa 439.1873, found 439.1907.
1
9
32 2 6