Реакция #2200588

Уравнение реакции

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

Растворители

methanol

CHCl3

dichloromethane

Условия реакции

Обработка

1. 1
   workup.WAITto room temperature for 22 hours
2. 2
   Другоеthe reaction mixture was separated in saturated NaHCO3 and in ether
3. 3
   ЭкстракцияThe aqueous phase was extracted with ether
4. 4
   Промывкаthe ether extracts were washed with brine, they
5. 5
   Другоеwere dried
6. 6
   Фильтрацияfiltered on a short disk of Celite and Na2SO4
7. 7
   Другоеevaporated
8. 8
   ДругоеFlash chromatography on a silica gel column with, as eluent, a heptane/EtOAc=3:1 then 2:1 mixture produced

Методика

(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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