2-(Bromomethyl)benzonitrile → t-Butyl (2S,3R,5R)-5-(2-cyanobenzyl)-6-oxo-2,3-diphenyl-4-morpholine carboxylate

HRID 1078150노트

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HRID 1078150 반응식
[O:1]=[C:2]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:4]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:3]1.Br[CH2:28][C:29]1[C:30]([C:35]#[N:36])=[CH:31][CH:32]=[CH:33][CH:34]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>O1CCCC1>[C:35]([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[CH2:28][C@H:7]1[N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:5]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C@H:4]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[O:3][C:2]1=[O:1])#[N:36]

참가 물질

5

반응물 3

HCID 895992-(Bromomethyl)benzonitrileHCID 9812251,1-Dimethylethyl (2S,3R)-6-oxo-2,3-diphenyl-4-morpholinecarboxylateHCID 2724254Sodium bis(trimethylsilyl)amide

생성물 1

HCID 53819028t-Butyl (2S,3R,5R)-5-(2-cyanobenzyl)-6-oxo-2,3-diphenyl-4-morpholine carboxylate수율 63%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-78 °C

실험 절차

To a stirred solution of 9.68 g (27.4 mmol) of t-butyl (2S,3R)-(+)-6-oxo-2,3-diphenyl-4-morpholine carboxylate (Aldrich Chemical Company) and 5.91 g (30.1 mmol, 1.1 eq) of α-bromo-o-tolunitrile in 140 mL of tetrahydrofuran at -78° C. was added dropwise 28.8 mL of a 1.0M THF solution of sodium hexamethyldisilazide (28.8 mmol) over 15 min. The mixture was stirred at -78° C. for 3 h, then quenched with saturated aqueous ammonium chloride, extracted with ethyl acetate (5×150 mL) and the combined organic extracts washed with water, saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated under reduced pressure. Chromatography on silica gel (elution with 20% ethyl acetate-hexanes) gave the product as a white solid (8.01 g, 63%). 1H NMR indicates this compound exists as an approximately 5:1 mixture of rotamers. 1H NMR (400 MHz, CDCl3): major rotamer--δ0.92 (s, 9H), 3.52 (dd; 10, 14 Hz; 1H), 3.62 (dd; 5, 14 Hz; 1H), 5.08 (d, 3 Hz, 1H), 5.40 (dd; 5, 10 Hz; 1H); 5.79 (d, 3 Hz, 1H), 6.52 (d, 8 Hz, 2H), 6.92 (d, 8 Hz, 2H), 7.00-7.70 (m, 1 OH). FAB-MS: calculated for C29H28N2O4 468; found 469 (M+H,30%), 369 (M-BOC, 100%).

후처리

  1. customquenched with saturated aqueous ammonium chloride
  2. extractionextracted with ethyl acetate (5×150 mL)
  3. washthe combined organic extracts washed with water, saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure

출처 및 근거

ORD 기록
ord-f0e0a2dcbd5645d29f2b22897baac7d0
출처 데이터셋
uspto-grants-1996_08
특허 번호
US05545735

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