1,1-Dimethylethyl (2S,3R)-6-oxo-2,3-diphenyl-4-morpholinecarboxylate → tert-Butyl (3R,5R,6S)-2-oxo-5,6-diphenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine-4-carboxylate

HRID 579477노트

반응식

HRID 579477 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.I[CH2:28][CH2:29][CH2:30][CH2:31][B:32]1[O:36][C:35]([CH3:38])([CH3:37])[C:34]([CH3:40])([CH3:39])[O:33]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C>[O:1]=[C:2]1[O:3][C@@H:4]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C@@H:5]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@@H:7]1[CH2:28][CH2:29][CH2:30][CH2:31][B:32]1[O:36][C:35]([CH3:38])([CH3:37])[C:34]([CH3:39])([CH3:40])[O:33]1

참가 물질

6

반응물 3

HCID 9812251,1-Dimethylethyl (2S,3R)-6-oxo-2,3-diphenyl-4-morpholinecarboxylateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 668332412-(4-Iodobutyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

생성물 1

HCID 66833293tert-Butyl (3R,5R,6S)-2-oxo-5,6-diphenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine-4-carboxylate수율 94%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 12679Hexamethylphosphoramide용매

실험 절차

A solution of (2S,3R)-tert-butyl 6-oxo-2,3-diphenylmorpholine-4-carboxylate (4.69 g, 13.27 mmol) and 2-(4-iodobutyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (d 1.38, 5.96 mL, 8.23 g, 26.5 mmol, 2 equiv) in THF (66 mL, 0.2 M) and HMPA (6.6 mL) was cooled to −78° C. and treated with sodium bis(trimethylsilyl)amide (14.6 mL, 1.0 M, 1.1 equiv) drop wise over 5 min and stirred for 1 h. After warming to room temperature and stirring for an additional 2 h, the solution was cooled to 0° C. and quenched with 0.5 NHC (2-3 equiv). The resulting solution was diluted with heptane and washed successively with water and saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. Purification by MPLC (1-60% ethyl acetate in heptane over 6 CV) gave (3R,5R,6S)-tert-butyl 2-oxo-5,6-diphenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine-4-carboxylate as a white solid (6.66 g, 94%); ESI-LCMS m/z calcd for C31H42BNO2: expected 535.3. found 536.4 (M+H)+.

후처리

  1. stirringstirring for an additional 2 h
  2. temperaturethe solution was cooled to 0° C.
  3. customquenched with 0.5 NHC (2-3 equiv)
  4. additionThe resulting solution was diluted with heptane
  5. washwashed successively with water and saturated aqueous NaCl
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by MPLC (1-60% ethyl acetate in heptane over 6 CV)

출처 및 근거

ORD 기록
ord-9aa567abac124612a8f014bc75734f4d
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09040703B2

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