Acetaldehyde → [(S)-7-Cyano-4-((2R,3S)-3-hydroxy-1-ethyl-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester

HRID 449842Notes

Reaction equation

HRID 449842 reaction equation
[CH:1]([O:4][C:5](=[O:28])[NH:6][C@@H:7]1[CH2:27][C:10]2[N:11]([CH2:20][C@@H:21]3[C@@H:25]([OH:26])[CH2:24][CH2:23][NH:22]3)[C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2].[CH:29](=O)[CH3:30].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(#N)C.ClCCl>[CH:1]([O:4][C:5](=[O:28])[NH:6][C@@H:7]1[CH2:27][C:10]2[N:11]([CH2:20][C@@H:21]3[C@@H:25]([OH:26])[CH2:24][CH2:23][N:22]3[CH2:29][CH3:30])[C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 177AcetaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 66933386[(S)-7-Cyano-4-((2R,3S)-3-hydroxy-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester

Product 1

HCID 66933509[(S)-7-Cyano-4-((2R,3S)-3-hydroxy-1-ethyl-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl esterYield 31.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of [(S)-7-cyano-4-((2R,3S)-3-hydroxy-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester (300 mg, 784.4 μmol) in acetonitrile (20 mL) is treated with acetaldehyde (1.0 mL, 17.80 mmol) and sodium triacetoxyborohydride (520 mg, 2.35 mmol) and stirred at room temperature overnight. The suspension is treated with saturated sodium bicarbonate solution (40 mL) and stirred for 30 min. The resulting suspension is diluted with dichloromethane (100 mL) and washed with water (3×100 mL) and brine. The organic portion is dried over sodium sulfate, filtered, and concentrated to dryness. The resulting residue is purified by medium pressure liquid chromatography, eluting with methanol:chloroform (5:95). Fractions containing pure product are combined and concentrated to afford 0.1 g (31%) of the title compound. LC-ES/MS m/z 144.2 [M+H]+, TR=1.94 min.

Workup

  1. stirringstirred for 30 min
  2. washwashed with water (3×100 mL) and brine
  3. dry with materialThe organic portion is dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe resulting residue is purified by medium pressure liquid chromatography
  7. washeluting with methanol:chloroform (5:95)
  8. additionFractions containing pure product
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c8dc6ca7eba14d159d0c7bc7b4248013
Source dataset
uspto-grants-2013_07
Patent number
US08486943B2

Reaction notes

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