ÐÏࡱáration of compound 8 To a solution of 7 (24.0 g, 124 mmol) in
anhydrous methanol (400 mL) was slowly added sodium borohydride (23.4 g,
618 mmol) at 0oC. The reaction temperature was allowed to rise to room
temperature. After the reaction mixture was stirred for 4 hours, it was
concentrated under reduced pressure. Then the mixture was transferred to a
separatory funnel, and distilled water (400 mL) was added. After extraction
with ethyl acetate (400 mL X 4), the organic solution was dried over
anhydrous MgSO4, filtered, and concentrated to give a pale yellow oil (17.2
g, 106 mmol) : 1H NMR (300 MHz, CDCl3) 1.44 (s, 6H), 2.52 (br s, 2H),
3.69~3.82 (m, 4H), 4.00~4.01 (m, 2 H) Preparation of compound 9 To a
solution of 8 (17.2 g, 106 mmol) in acetonitrile (300 mL) were added
triethylamine (34.0 mL, 244 mmol), lithium chloride (40.0 g, 944 mmol), and
methanesulfonyl chloride (17.3 mL, 224 mmol) in sequence at 0oC. After
stirring for 30 minutes, the reaction mixture was heated to reflux
overnight. Then the mixture was concentrated under reduced pressure and
extracted with ethyl acetate (500 mL X 2) from aqueous sodium bicarbonate
solution. After being dried over anhydrous MgSO4, the mixture was filtered
and concentrated to give a dark brown liquid. The nonpolar dark brown
impurity was separated by extraction of the liquid with water (200 mL) and
n-hexane (200 mL). After extraction of the aquous solution with ethyl
acetate (200x4 mL), the ethyl acetate solution was dried over anhydrous
MgSO4, filtered, and conce1. Preparation of
N-(1,4-Dichloro-2(S)-hydroxy-3(R)-butyl)phthalimide (11) A mixture of
1,4-dichlorobutane-2(S),3(S)-diol sulfate (57.2 mg, 0.258 mmol) and
phthalimide potassium salt (51.4 mg, 0.272 mmol) in dry DMF (1.3 mL) was
stirred under nitrogen atmosphere at rt for 1 h. Solvent was removed under
reduced pressure. The residue was dissolved with dry THF (3 mL). To the
resulting solution were added conc. H2SO4 (13 4, 1168, 1010, 597 cm-1; mp
142~145 oC; HRMS (CI) m/z calcd 258.0664 for [M+H]+ C9H18NO3Cl2 found
258.0669. Preparation of
2(S)-t-Butyldimetylsilyloxy-3(R)-(t-butyloxycarbonyl)amino-1,4-dichlorobutane
(13a) To a stirred solution of 12 (100.0 mg, 0.389 mmol) in dry DMF (2.5
mL) were added imidazole (79.4 mg, 1.67 mmol), DMAP (4.8 mg, 0.039 mmol)
and tert-butyldimethylsilyl chloride (175.9 mg, 1.167 mmol) at room
temperature under N2. The resulting solution was stirred at 50oC for 12 h.
The reaction mixture was diluted with EtOAc (30 mL), washed with 0.1 N
citric acid solution (5 mL), sat aq NaHCO3 (5 mL), water (5 mL) and brine
(5 mL), and dried over anhydrous magnesium sulfate, filtered, concentrated
and column-chromatographed (10 % EtOAc in n-Hex) to provide
2(S)-t-butyldimetylsilyloxy-3(R)-(t-butyloxycarbonyl)amino-1,4-dichlorobutane
as a colorless solid (144.6mg, quantitative): Rf (silica gel; 10 % EtOAc in
n-Hex) 0.52; mp 73oC; 1H-NMR (300 MHz, , CDCl3)v4 X¼9QWô_R