Triethylamine → (1S,2S)-2-amino-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol

HRID 132937

반응식

HRID 132937 반응식
C(O[C@H:5]1[CH2:9][N:8](C(OC(C)(C)C)=O)[C@@H:7]([CH2:17]O)[CH2:6]1)C=C.F[C:20]1[CH:21]=[C:22]([CH:55]=[C:56](F)[CH:57]=1)[CH2:23][C@H:24](C(N1[C@@H](CC2C=CC=CC=2)COC1=O)=O)[C@@H:25]([CH:27]1[CH2:32][CH2:31][CH2:30]CN1C(OC(C)(C)C)=O)O.C([C@H]1COC(=O)N1[C:72](=[O:83])[CH2:73][CH2:74][C:75]1[CH:80]=[C:79]([F:81])[CH:78]=[C:77]([F:82])[CH:76]=1)C1C=CC=CC=1.B(OS(C(F)(F)F)(=O)=O)(CCCC)CCCC.C([N:103](CC)CC)C.C(O[C@H]1CN(C(OC(C)(C)C)=O)[C@@H](C(O)=O)C1)C=C>C(Cl)Cl.CO>[NH2:103][C@@H:73]([CH2:74][C:75]1[CH:76]=[C:77]([F:82])[CH:78]=[C:79]([F:81])[CH:80]=1)[C@@H:72]([C@H:9]1[CH2:5][CH2:6][CH2:17][CH2:7][N:8]1[CH:23]([C:22]1[CH:21]=[CH:20][CH:57]=[CH:56][CH:55]=1)[C:24]1[CH:25]=[CH:27][CH:32]=[CH:31][CH:30]=1)[OH:83]

참가 물질

9

반응물 6

HCID 8471TriethylamineHCID 2724243Methanesulfonic acid, 1,1,1-trifluoro-, anhydride with B,B-dibutylborinic acidHCID 59733915(S)-4-benzyl-3-(3-(3,5-difluorophenyl)propanoyl)oxazolidin-2-oneHCID 67315699(4R)-1-Boc-4-(2-propen-1-yloxy)-D-prolineHCID 67315914(2R,4R)-tert-butyl 4-(allyloxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylateHCID 69196027tert-butyl 2-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)piperidine-1-carboxylate

생성물 1

HCID 58608199(1S,2S)-2-amino-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매2회

반응 조건

온도
-78 °C

실험 절차

Step I (3): Preparation of tert-butyl 2-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)piperidine-1-carboxylate. To a solution of (S)-4-benzyl-3-(3-(3,5-difluorophenyl)propanoyl)oxazolidin-2-one (Preparation M, 2.2 g, 6.57 mmol) in CH2Cl2 (100 mL) at −78° C. was added Bu2BOTf (di-n-butylboron triflate) (7.9 ml, 7.9 mmol, 1M in CH2Cl2) and triethyl amine (1.4 mL, 10 mmol). The resulting mixture was brought up to 0° C. and stirred for 20 min. The mixture was cooled back to −78° C. and a solution of tert-butyl 2-formylpiperidine-1-carboxylate (Step I (2), 1.4 g, 6.57 mmol) in CH2Cl2 (100 mL) was added. When the addition was complete, the mixture was allowed to warm to and stirred at rt overnight. MeOH was added and the mixture was concentrated in vacuo. The crude mixture was purified by silica gel Flash chromatography to give 2.0 g of the title compound: 1H NMR (CDCl3, 500 MHz) δ 1.42-1.66 (14H, m), 1.86-2.26 (1H, m), 2.62-3.40 (6H, m), 3.84-4.69 (7H, m), 6.58-6.65 (1H, m), 6.81-6.85 (2H, m), 6.90-6.96 (2H, m), 7.22-7.27 (3H, m). MS (ESI) (M+Na)+ 581.12.

후처리

  1. customwas brought up to 0° C.
  2. additionWhen the addition
  3. temperatureto warm to and
  4. stirringstirred at rt overnight
  5. concentrationthe mixture was concentrated in vacuo
  6. customThe crude mixture was purified by silica gel Flash chromatography

출처 및 근거

ORD 기록
ord-f515ed98c4e14f248530b3e0e0c654c8
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07388007B2

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