3-(Methylthio)-1-propanol → Ethyl 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-(3-(methylthio)propoxy)phenyl)-1H-pyrrole-2-carboxylate

HRID 1507742Notes

Reaction equation

HRID 1507742 reaction equation
[CH2:1]([O:8][C:9]1[C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:12]([C:22](=[O:26])[N:23]([CH3:25])[CH3:24])[N:11]([C:27]2[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=2)[C:10]=1[C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:39][S:40][CH2:41][CH2:42][CH2:43]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[CH2:1]([O:8][C:9]1[C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:12]([C:22](=[O:26])[N:23]([CH3:25])[CH3:24])[N:11]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH2:43][CH2:42][CH2:41][S:40][CH3:39])=[CH:29][CH:28]=2)[C:10]=1[C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 104483-(Methylthio)-1-propanol2×HCID 11776Triphenylphosphine2×HCID 5363146Diisopropyl azodicarboxylate2×HCID 117642662Ethyl 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-hydroxyphenyl)-1H-pyrrole-2-carboxylate

Product 1

HCID 117642705Ethyl 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-(3-(methylthio)propoxy)phenyl)-1H-pyrrole-2-carboxylateYield 94.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-hydroxyphenyl)-1H-pyrrole-2-carboxylate (36) (350 mg, 0.68 mmol) in THF (2 mL) at 0° C. was added 3-(methylthio)propan-1-ol (84 μL, 0.82 mmol), triphenylphosphine (214 mg, 0.82 mmol), and DIAD (159 μL, 0.82 mmol). After 2 h further portions of 3-(methylthio)propan-1-ol (84 μL, 0.82 mmol), triphenylphosphine (214 mg, 0.82 mmol) and DIAD (159 μL, 0.82 mmol) were added, and the reaction mixture was allowed to stir at RT for 4 days. The reaction mixture was quenched with water (10 mL) and extracted with EtOAc (2×20 mL), the combined organics were washed with brine (30 mL), dried (MgSO4) filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (12 g, 0-100% EtOAc in isohexane) to afford ethyl 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-(3-(methylthio)propoxy)phenyl)-1H-pyrrole-2-carboxylate (43) (389 mg, 85%) as a clear yellow oil: m/z 603 (M+H)+ (ES+).

Workup

  1. customThe reaction mixture was quenched with water (10 mL)
  2. extractionextracted with EtOAc (2×20 mL)
  3. washthe combined organics were washed with brine (30 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica gel chromatography (12 g, 0-100% EtOAc in isohexane)

Sources & evidence

ORD record
ord-3d7ea25244d843f48fa5cfd254edfaf6
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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