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Tetrahydrofuran → tert-butyl{(1S,2R)-2-azido-2-[3,5-bis(trifluoromethyl)phenyl]-1-methylethyl}{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

HRID 1994510
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HRID 1994510 반응식
C1(P([N:15]=[N+:16]=[N-:17])(C2C=CC=CC=2)=O)C=CC=CC=1.[C:18]([O:22][C:23](=[O:65])[N:24]([C@@H:47]([CH3:64])[C@H:48]([C:50]1[CH:55]=[C:54]([C:56]([F:59])([F:58])[F:57])[CH:53]=[C:52]([C:60]([F:63])([F:62])[F:61])[CH:51]=1)O)[CH2:25][C:26]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=1C1C=C(C(C)C)C=CC=1OC)([CH3:21])([CH3:20])[CH3:19].C1C=CC(P([C:79]2[CH:84]=[CH:83][CH:82]=[CH:81]C=2)C2C=CC=CC=2)=CC=1.N(C(OCC)=O)=N[C:87](OCC)=O.[CH2:97]1[CH2:101][O:100][CH2:99][CH2:98]1>CCOC(C)=O>[C:18]([O:22][C:23](=[O:65])[N:24]([C@@H:47]([CH3:64])[C@H:48]([N:15]=[N+:16]=[N-:17])[C:50]1[CH:51]=[C:52]([C:60]([F:62])([F:61])[F:63])[CH:53]=[C:54]([C:56]([F:57])([F:58])[F:59])[CH:55]=1)[CH2:25][C:26]1[CH:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[CH:28][C:27]=1[C:97]1[CH:98]=[C:83]([CH:82]([CH3:81])[CH3:87])[CH:84]=[CH:79][C:101]=1[O:100][CH3:99])([CH3:19])([CH3:20])[CH3:21]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 5

HCID 8028Tetrahydrofuran2회HCID 11776Triphenylphosphine2회HCID 199401P,P-Diphenylphosphinic azide2회HCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 87121496Tert-butyl{(1s,2s)-2-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-1-methylethyl}{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

생성물 1

HCID 86603415tert-butyl{(1S,2R)-2-azido-2-[3,5-bis(trifluoromethyl)phenyl]-1-methylethyl}{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

A dry flask was charged with THF (1 mL) diethyl azodicarboxylate (DEAD) (11 μL, 0.0698 mmol) and diphenylphosphoryl azide (DPPA) (15 μL, 0.0698 mmol). tert-butyl{(1S,2S)-2-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-1-methylethyl}{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (20.7 mg, 0.0698 mmol) was added by cannula in THF (1 mL). Next Ph3P (18.3 mg, 0.0698 mmol) was added. The reaction was stirred at room temperature for 30 min, and then additional DEAD (11 μL, 0.0698 mmol), DPPA (15 μL, 0.0698 mmol), and Ph3P (18.3 mg, 0.0698 mmol) were added. After an additional 30 min, the reaction was diluted with EtOAc (40 mL) and washed with water and brine (15 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 15% EtOAc/hexanes afforded tert-butyl{(1S,2R)-2-azido-2-[3,5-bis(trifluoromethyl)phenyl]-1-methylethyl}{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate. Rf=0.60 (25% EtOAc/hexanes). LCMS=619.3 (M+1−BOC)+.

후처리

  1. waitAfter an additional 30 min
  2. washwashed with water and brine (15 mL each)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the residue by flash chromatography with 15% EtOAc/hexanes

출처 및 근거

ORD 기록
ord-55052fbf903543fca87f9601c5f2451b
출처 데이터셋
uspto-grants-2010_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07652049B2

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