8
K. CH GHOSH ET AL.
under reduced pressure to give the title compound 22 as slightly yellow oil (450 mg,
99%). The crude product was used in the next step without further purification.
1H NMR (500 MHz, CDCl3) d 7.35–7.26 (m, 5H), 4.03 (m, 1H), 3.71 (m, 1H), 3.55
(t, J ¼ 9.5 Hz, 1H), 2.49–2.34 (m, 3H); 13C NMR (125 MHz, CDCl3) d 142.7, 128.7,
127.6, 126.6, 68.1, 57.5; IR (Neat) ꢀmax 3367, 3064, 1602, 1492, 1215 cmꢁ1; HRMS (ESI):
m/z [M þ H]þ calcd for C8H12NO: 138.0913; found: 138.0911.[32]
Benzyl (2-hydroxy-1-phenylethyl)carbamate (23)
To a solution of 22 (778 mg, 5.67 mmol) and DMAP (7 mg, 0.056 mmol) in DCM
(20 mL) was added dropwise benzyl chloroformate (971 lL, 60 mmol) at 0 ꢀC, followed
by Et3N (1.98 mL, 14.2 mmol). The resulting mixture was stirred at room temperature
for overnight. The solvent was evaporated. The reaction mixture was extracted with
EtOAc and the combined organic layers were washed with H2O and brine, dried over
anhydrous Na2SO4, and evaporated under reduced pressure. Crude product was purified
by column chromatography using EtOAc-pet ether (3:7) on silica gel to afford 23 as a
1
colorless oil (1.16 g, 76% yield). H NMR (300 MHz, CDCl3) d 7.32–7.24 (m, 10H), 5.75
(s, 1H), 5.07 (s, 2H), 4.81 (s, 1H), 3.77 (s, 2H), 2.77 (br s, 1H); 13C NMR (75 MHz,
CDCl3) d 156.6, 139.3, 136.4, 128.9, 128.6, 128.3, 127.9, 126.7, 67.1, 66.4, 57.2; IR (Neat)
ꢀmax 3365, 2931, 2106, 1734, 1109 cmꢁ1; HRMS (ESI): m/z [M þ Na]þ calcd for
C16H17NO3Na: 294.1106; found: 294.1107.[32]
Methyl 2-(((benzyloxy)carbonyl)amino)-2-phenylacetate (24)
To a solution of the alcohol 23 (310 mg, 1.14 mmol) in EtOAc (15 mL) was added 2-
iodoxybenzoic acid (IBX) (640 mg, 2.29 mmol) portion wise, and it was refluxed for 2 h
in open atmosphere. After completion of the reaction (TLC), the mixture was cooled to
room temperature and filtered through a celite pad. Solvent removal under reduced
pressure afforded the crude aldehyde (307 mg) which was used in the next step without
further purification.
To a solution of the above crude aldehyde in t-BuOH (6 mL) and 2-methyl-2-butene
(3 mL) was added a solution of NaClO2 (465 mg, 5.14 mmol) and NaH2PO4 (475 mg,
3.43 mmol) in H2O (3 mL) at 0 ꢀC. The reaction mixture was stirred for 2 h at room
temperature and diluted with saturated aqueous NH4Cl solution (1 mL). The organic
layer was extracted with EtOAc (3 ꢂ 5 mL). The combined organic layers were dried, fil-
tered, and concentrated in vacuo to give the crude product which was purified by silica
gel column chromatography, eluting with DCM-MeOH (97:3), to afford the correspond-
ing acid as white foam (291 mg). Product was confirmed by mass spectrometry. HRMS
(ESI): m/z [M þ Na]þ calcd for C16H15NO4Na: 308.0899; found: 308.0898.
The free acid (291 mg, 1.02 mmol) was then dissolved in diethyl ether (5 mL, min-
imum volume). Diazomethane in diethyl ether was added slowly at 0 ꢀC until a yellow
color persisted (monitored by TLC). Removal of ether followed by silica gel column
chromatography purification using EtOAc—petroleum ether (1:4) gave the product
24 as colorless to faint yellow oil (185 mg, 55%, after 3 steps from amino alcohol 23).
1H NMR (300 MHz, CDCl3) d 7.39–7.31 (m, 10H), 5.99 (d, J ¼ 7.5 Hz, 1H), 5.42