Phenol → 3-Phenoxy-hexahydro-pyrrolo[3,2-b]pyrrole-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester

HRID 1965159노트

반응식

HRID 1965159 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([OH:13])[CH:10]2[N:14]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[CH2:15][CH2:16][CH:9]12)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:27]1(O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:10]2[N:14]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[CH2:15][CH2:16][CH:9]12)=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

6

반응물 4

HCID 996PhenolHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 676073943-Hydroxy-hexahydro-pyrrolo[3,2-b]pyrrole-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester

생성물 1

HCID 676086123-Phenoxy-hexahydro-pyrrolo[3,2-b]pyrrole-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester수율 47%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 11 (600 mg, 1.65 mmol) in THF (10 mL) was added phenol (186 mg, 1.98 mmol) and Ph3P (520 mg, 1.98 mmol). DIAD (459 mg, 2.31 mmol) was then added and the reaction mixture was immersed into a preheated (75° C.) oil bath. After 16 h, the reaction mixture was concentrated in vacuo and the residue was passed through a short column of silica gel (4:1 hexanes/EtOAc). The crude product was then purified by reverse-phase HPLC (2″ Dynamax® C18, 10-70% ACN/water containing 0.1% HOAc over 30 min; Flow: 40 mL/min) to afford 340 mg (46%) of 12 as a white solid. 1H NMR (CDCl3, 300 MHz), mixture of rotomers: δ7.37-7.27 (m, 6H), 7.22 (m, 1H), 7.04 (m, 1H), 6.96-6.88 (m, 1H), 6.81 (d, J=8.4 Hz, 1H), 5.27-5.13 (m, 2H), 5.01 (dd, J=3.3, 6.3 Hz, 0.5H), 4.77 (d, J=2.7 Hz, 0.5H), 4.57-4.45 (m, 1H), 4.43-4.32 (m, 1H), 3.99-3.89 (m, 1H), 3.85-3.73 (m, 1H), 3.37 (m, 1H), 3.21 (dt, J=5.7, 11.7 Hz, 1H), 2.38 (m, 0.5H), 2.23 (dd, J=5.7, 13.2 Hz, 0.5H), 1.91-1.83 (m, 1H), 1.47 (m, 9H) ppm. Mass spectrum, m/z [339.2] (M−Boc)+.

후처리

  1. customwas immersed into a preheated (75° C.) oil bath
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customThe crude product was then purified by reverse-phase HPLC (2″ Dynamax® C18, 10-70% ACN/water containing 0.1% HOAc over 30 min

출처 및 근거

ORD 기록
ord-c3a42f0c1e354661bd44d30414d0aa8a
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415486B2

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