4-Methylmorpholine → tert-Butyl 3-(4-(tert-butoxycarbonylamino)-1H-indol-1-yl)-3-(4-chlorophenyl)-4-hydroxybutanoate

HRID 1427287Notes

Reaction equation

HRID 1427287 reaction equation
[C:1]([O:5][C:6](=[O:36])[CH2:7][C:8]([N:19]1[C:27]2[C:22](=[C:23]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH:24]=[CH:25][CH:26]=2)[CH:21]=[CH:20]1)([C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)[C:9](O)=[O:10])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(Cl)(=O)OCC(C)C.[BH4-].[Na+]>COCCOC>[C:32]([O:31][C:29]([NH:28][C:23]1[CH:24]=[CH:25][CH:26]=[C:27]2[C:22]=1[CH:21]=[CH:20][N:19]2[C:8]([C:12]1[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=1)([CH2:9][OH:10])[CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:36])=[O:30])([CH3:33])([CH3:34])[CH3:35]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 705646004-tert-butoxy-2-(4-(tert-butoxycarbonylamino)-1H-indol-1-yl)-2-(4-chlorophenyl)-4-oxobutanoic acid

Product 1

HCID 86705056tert-Butyl 3-(4-(tert-butoxycarbonylamino)-1H-indol-1-yl)-3-(4-chlorophenyl)-4-hydroxybutanoate

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of the product of step B (1.5 g, 2.9 mmol) and NMM (590 mg, 5.83 mmol) in DME (15 mL) was added isobutyl carbonochloridate (793 mg, 5.83 mmol) dropwise at 0° C. After stirring for 30 min. NaBH4 was added to the mixture at 0° C. The resulting mixture was stirred at room temperature for another 1 h, and then quenched with saturated ammonium chloride solution (10 mL), extracted with ethyl acetate. The organic layers were washed with brine (10 mL), dried over sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography (PE:EA=3:1) to afford the title compound as colorless oil. LC/MS m/z=501.2[M+H]+.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for another 1 h
  2. customquenched with saturated ammonium chloride solution (10 mL)
  3. extractionextracted with ethyl acetate
  4. washThe organic layers were washed with brine (10 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by silica gel chromatography (PE:EA=3:1)

Sources & evidence

ORD record
ord-bf5c4756065b461e982a5e30e3ab1ac1
Source dataset
uspto-grants-2015_01
Patent number
US08933113B2

Reaction notes

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