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

HRID 1965159Notes

Reaction equation

HRID 1965159 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-c3a42f0c1e354661bd44d30414d0aa8a
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

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