反応 #2200588

反応方程式

TMSCN

(R)-phenylglycinol

(2S,3S)-2-methyl-3-tetrahydropyranyloxybutyraldehyde

(2S,3S)-2-methyl-3-benzyloxybutyraldehyde

(1R,2R,3S)-1-cyano-2-methyl-3-tetrahydropyranyloxy-N-[(R)-1′-phenyl-2′-hydroxyethyl]butylamine

(1S,2R,3S)-1-cyano-2-methyl-3-tetrahydropyranyloxy-N-[(R)-1′-phenyl-2′-hydroxyethyl]butylamine

→

(2R,3S)-1-cyano-2-methyl-3-tetrahydropyranyloxy-N-[(R)-1′-phenyl-2′-hydroxyethyl]butylamine

溶媒

methanol

CHCl3

dichloromethane

反応条件

後処理

1. 1
   workup.WAITto room temperature for 22 hours
2. 2
   その他the reaction mixture was separated in saturated NaHCO3 and in ether
3. 3
   抽出The aqueous phase was extracted with ether
4. 4
   洗浄the ether extracts were washed with brine, they
5. 5
   その他were dried
6. 6
   ろ過filtered on a short disk of Celite and Na2SO4
7. 7
   その他evaporated
8. 8
   その他Flash chromatography on a silica gel column with, as eluent, a heptane/EtOAc=3:1 then 2:1 mixture produced

実験手順

(R)-phenylglycinol (115 mg, 0.84 mmol) was added at room temperature to a solution of (2S,3S)-2-methyl-3-tetrahydropyranyloxybutyraldehyde (6) (130 mg, 0.7 mmol) in dichloromethane (6 ml), and the stirring was continued for 2 hours at room temperature. The reaction mixture was cooled to 0° C., and methanol (2 ml) and TMSCN (104 mg, 140 μl, 1.05 mmol) were successively introduced. After stirring at 0° C. for 2 hours and then to room temperature for 22 hours, the reaction mixture was separated in saturated NaHCO3 and in ether. The aqueous phase was extracted with ether, the ether extracts were washed with brine, they were dried and filtered on a short disk of Celite and Na2SO4 and then evaporated. Flash chromatography on a silica gel column with, as eluent, a heptane/EtOAc=3:1 then 2:1 mixture produced a mixture of (1R,2R,3S)-1-cyano-2-methyl-3-tetrahydropyranyloxy-N-[(R)-1′-phenyl-2′-hydroxyethyl]butylamine (1R)-(19) and (1S,2R,3S)-1-cyano-2-methyl-3-tetrahydropyranyloxy-N-[(R)-1′-phenyl-2′-hydroxyethyl]butylamine (1S)-(19) (225 mg in total, 97%): IR (CHCl3) 3630, 3442, 3347, 3012, 2947, 2856, 1493, 1455, 1385, 1356, 1231, 1173 cm−1; 1H NMR (250 MHz, CDCl3) δ 7.37 to 7.27 (m, 5H); 4.72 to 4.39 (m, 1H); 4.14 to 3.39 (m, 7H); 2.30 (broad s, 2H, OH+NH); 2.05 to 1.20 (m, 7H); [1.17 (d, J=6.3 Hz), 1.08 (d, J=7.7 Hz), 1.05. (d, J=7.0 Hz), 6H]; 13C NMR (62.5 MHz, CDCl3) δ 140.6; 140.0; 138.7; 138.4; 128.6; 128.0; 127.8; 127.7; 127.3; 120.4; 119.8; 119.6; 119.2; 101.0; 100.1; 97.5; 95.6; 78.9; 76.3; 71.4; 71.2; 67.1; 66.9; 66.0; 65.6; 65.5; 63.2; 63.0; 62.8; 62.7; 53.0; 50.5; 50.1; 49.9; 42.7; 42.5; 42.3; 31.0; 30.8; 30.6; 25.2; 25.0; 21.6; 20.0; 19.6; 19.4; 18.3; 17.0; 16.1; 14.0; 12.7; 12.0; 11.7. MS (CI) m/z 333 [M+H]+. HRMS: calculated for C19H29N2O3 (M+H), 333.21780; found, 333.21668.

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