Diethyl Ether → HCID 10453438, compound
Reaction equation
O=[C:2]1[C@@:19]2([CH3:20])[C:6]([NH:7][CH2:8][C@@H:9]3[C@@H:18]2[CH2:17][CH2:16][C@@:14]2([CH3:15])[C@H:10]3[CH2:11][CH2:12][CH2:13]2)=[CH:5][C:4](=[O:21])[CH:3]1CCC1CCCCC1.CC[O:32][CH2:33][CH3:34]>>[O:32]=[C:33]([C@H:13]1[CH2:12][CH2:11][C@H:10]2[C@H:9]3[C@H:18]([CH2:17][CH2:16][C@:14]12[CH3:15])[C@:19]1([CH3:20])[C:6](=[CH:5][C:4](=[O:21])[CH2:3][CH2:2]1)[NH:7][CH2:8]3)[CH2:34][CH:2]1[CH2:19][CH2:6][CH2:5][CH2:4][CH2:3]1Participants
Procedure
A solution of 17β-carboxy-6-t-butoxycarbonyl-6-azaandrost-4-en-3-one (260 mg, 0.62 mmol), example 1, part F, is dissolved in toluene (10 mL) and treated with pyridine (3 eq) and catalytic dimethylformamide, cooled to 0° C., and thionyl chloride added (80 mL, 1.10 mmol). The reaction is then allowed to warm to room temperature and stir for 1 hr. The solids are then removed by filtration, the solution concentrated, the resulting crude acrid chloride dissolved in THF (6 mL), Cul added (120 mg, 0.62 mmol), cooled to -78° C. and treated with methylenecyclo-hexylmagnesium bromide (2.0M in diethyl ether, 0.5 mL, 1 mmol). The reaction is allowed to warm to room temperature, stir for 30 min, is quenched with saturated NaHSO4, extracted with ethyl acetate (2×25 mL), dried over MgSO4, concentrated and chromatographed on silica gel (25% ethyl acetate/hexane) to give 17β-(1-oxo-2-(cyclohexylethyl))-6-t-butoxycarbonyl-6-azaan-drost-4-en-3-one; yield: 302 mg (98%). This material may be deprotected as described in example 1, part G above to give, on crystallization from ether, 17β-(1-oxo-2-(cyclohexylethyl)-6-azaandrost-4-en-3-one; yield: 121 mg (50%); m.p. 214°-216° C. Anal. Calcd. for C26H39 NO2. 1/2H2O; C, 76.80; H, 9.92; N, 3.44. Found: C, 76.61; H, 9.89; N, 3.49.
Sources & evidence
- ORD record
- ord-c581fdf813574a3cb6d9652a25220861
- Source dataset
- uspto-grants-1998_01
- Patent number
- US05708001
Reaction notes
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