Water → HCID 54471193, compound

HRID 975014Notes

Reaction equation

HRID 975014 reaction equation
[BH4-].[Li+].[CH2:3]([O:10][C:11]([N:13]1[CH2:17][CH2:16][CH2:15][C@@H:14]1[C:18]([C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([O:29][CH3:30])[CH:27]=2)[NH:22][CH:21]=1)=O)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.O.C(OCC)(=O)C>O1CCCC1>[CH2:3]([O:10][C:11]([N:13]1[CH2:17][CH2:16][CH2:15][C@@H:14]1[CH2:18][C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([O:29][CH3:30])[CH:27]=2)[NH:22][CH:21]=1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 4148881Lithium borohydrideHCID 10429731HCID 10429731, compound

Product 1

HCID 54471193HCID 54471193, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred mixture of lithium borohydride (0.092 g, 4.22 mmol, 2 eq) in anhydrous tetrahydrofuran (5 mL) at 0° C. was added a solution of the (R)-3-(N-benzyloxycarbonylpyrrolidin-2-ylcarbonyl)-5-methoxy-1H-indole (0.80 g, 2.11 mmol) in anhydrous tetrahydrofuran (8 mL). The resultant mixture was heated at reflux under nitrogen for 1 hour. The reaction mixture was cooled, and water (1 mL) was added carefully, followed by ethyl acetate (20 mL). The resultant mixture was stirred at room temperature for 30 minutes, dried (MgSO4), filtered through diatomaceous earth, and the filtrate was evaporated under reduced pressure. The residue was column chromatographed using silica gel (approximately 50 g) and elution with ethyl acetate/hexanes [1:1] afforded (R)-3-(N-benzyloxycarbonylpyrrolidin-2-ylmethyl)-5-methoxy-1H-indole as a colorless gum: 13C NMR [Note: due to slow nitrogen inversion two conformers of the products are seen by NMR spectroscopy] (CDCl3) δ162.5, 136.9, 136.2, 128.4, 127.8, 127.6, 124.5, 123.3, 120.8, 120.3, 111.5, 66.8, 57.4, 39.5, 36.5, 31.4, 29.8, 25.8, 25.5, 18.8; LRMS (m/z, relative intensity) 364 (30, M+), 204 (17), 160 (92), 145 (17), 117 (13), 91 (100). Anal. calcd for C22H24N2O3.0.5 H2O : C, 70.76; H, 6.75; N, 7.50. Found: C, 70.70; H, 6.94; N,7.15.

Workup

  1. temperatureat reflux under nitrogen for 1 hour
  2. temperatureThe reaction mixture was cooled
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered through diatomaceous earth
  5. customthe filtrate was evaporated under reduced pressure
  6. customchromatographed
  7. washsilica gel (approximately 50 g) and elution with ethyl acetate/hexanes [1:1]

Sources & evidence

ORD record
ord-0a54b4da1ef243cd83d95c32a9ecfaf5
Source dataset
uspto-grants-1997_03
Patent number
US05607951

Reaction notes

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