Ammonium Sulfate → 1,5-bis(t-butoxycarbonyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid

HRID 352872Notes

Reaction equation

HRID 352872 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12][C:11]=2[CH:10]=[C:9]1[CH:24]=[O:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl([O-])=[O:27].[Na+].P([O-])(O)(O)=O.[Na+].S([O-])([O-])(=O)=O.[NH4+].[NH4+]>C(O)(C)(C)C.CC(=CC)C.O.C(OCC)C>[C:1]([O:5][C:6]([N:8]1[C:16]2[CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12][C:11]=2[CH:10]=[C:9]1[C:24]([OH:27])=[O:25])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 4

HCID 6097028Ammonium SulfateHCID 111522941,5-Bis(tert-butoxycarbonyl)-2-formyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridineHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphate

Product 1

HCID 113829881,5-bis(t-butoxycarbonyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6386tert-ButanolSolventHCID 105532-Methyl-2-buteneSolvent

Procedure

To a solution of 1,5-bis(t-butoxycarbonyl)-2-formyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine (44.0 mg) in t-butanol (2.0 ml), 2-methyl-2-butene (150 μl) and an aqueous solution (6.0 ml) of sodium chlorite (102 mg) and sodium dihydrogenphosphate (135 mg) were added at room temperature. After stirring for 21 hours, the reaction mixture was added with diethyl ether (10 ml) and water (10 ml), followed by the addition of ammonium sulfate until saturation. The resulting mixture was separated, followed by extraction with diethyl ether (10 ml). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure, whereby the residue, that is, 1,5-bis(t-butoxycarbonyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid was obtained as a white foamy substance. To a solution of the resulting residue in N,N-dimethylformamide (2.0 ml), methylene chloride (2.0 ml) and 1-[(6-chloronaphthalen-2-yl)sulfonyl]piperazine hydrochloride (55.0 mg) were dissolved, followed by the addition of 1-(dimethylaminopropyl)-3-ethyl carbodiimide (30.5 mg) and 1-hydroxybenzotriazole (21.5 mg) at room temperature. At 0° C., diisopropylethylamine (67.0 μl) was added thereto. After stirring overnight at room temperature, a 10% aqueous citric acid solution (10 ml) and methylene chloride (10 ml) were added to the reaction mixture to cause separation. The organic layer was extracted with methylene chloride (10 ml). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by thin-layer preparative chromatography on silica gel (methylene chloride:acetone=10:1) and the white solid thus obtained was reprecipitated in a methylene chloride—methanol—water system. After filtration and washing with water, the title compound (50.0 mg) was obtained as a colorless transparent caramel-like substance. IR(KBr)cm−1: 2981, 2929, 2860, 1743, 1693, 1647, 1456, 1421, 1367, 1348, 1325, 1279, 1236, 1165, 1103, 955, 945, 729.

Workup

  1. customThe resulting mixture was separated
  2. extractionfollowed by extraction with diethyl ether (10 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure, whereby the residue

Sources & evidence

ORD record
ord-d4c6b2f4c47c4d5d9f38dd59b9ed0c12
Source dataset
uspto-grants-2004_06
Patent number
US06747023B1

Reaction notes

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