Sodium triacetoxyborohydride → (R)-6-(2-(9-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)ethyl)-3-methylisochroman-1-one

HRID 2281346Notes

Reaction equation

HRID 2281346 reaction equation
[OH:1][C@H:2]([C:13]1[CH:22]=[CH:21][C:16]2[C:17](=[O:20])[O:18][CH2:19][C:15]=2[C:14]=1[CH3:23])[CH2:3][N:4]1[CH:9]2[CH2:10][NH:11][CH2:12][CH:5]1[CH2:6][O:7][CH2:8]2.[CH3:24][C@@H:25]1[CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([CH2:35][CH:36]=O)[CH:32]=2)[C:27](=[O:38])[O:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[OH:1][C@H:2]([C:13]1[C:14]([CH3:23])=[C:15]2[C:16](=[CH:21][CH:22]=1)[C:17](=[O:20])[O:18][CH2:19]2)[CH2:3][N:4]1[CH:9]2[CH2:10][N:11]([CH2:36][CH2:35][C:31]3[CH:32]=[C:33]4[C:28](=[CH:29][CH:30]=3)[C:27](=[O:38])[O:26][C@H:25]([CH3:24])[CH2:34]4)[CH2:12][CH:5]1[CH2:6][O:7][CH2:8]2

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 86693035[(3R)-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl]acetaldehyde2×HCID 1176420375-[(1R)-1-Hydroxy-2-(3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)ethyl]-4-methyl-2-benzofuran-1-(3H)-one2×

Product 1

HCID 71557350(R)-6-(2-(9-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)ethyl)-3-methylisochroman-1-one

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 5-[(1R)-1-hydroxy-2-(3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)ethyl]-4-methyl-2-benzofuran-1(3H)-one (INTERMEDIATE 17) (60 mg, 0.19 mmol) and (R)-2-(3-Methyl-1-oxoisochroman-6-yl)acetaldehyde (INTERMEDIATE 21) (39 mg, 0.19 mmol) in 1,2-dichloroethane (5 mL) was treated with sodium triacetoxyborohydride (120 mg, 0.57 mmol) and stirred at room temperature for 1 hour. The reaction mixture was concentrated and the residue was purified by preparative TLC eluting with 5% (10% NH4OH in MeOH)/95% DCM, followed by a second preparative TLC iteration eluting with 5% (10% NH4OH in MeOH)/95% chloroform (eluted twice) to provide (R)-6-(2-(9-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)ethyl)-3-methylisochroman-1-one.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was purified by preparative TLC
  3. washeluting with 5% (10% NH4OH in MeOH)/95% DCM
  4. washeluting with 5% (10% NH4OH in MeOH)/95% chloroform (
  5. washeluted twice)

Sources & evidence

ORD record
ord-1481c59432404e21bcb20ec378ff5db7
Source dataset
uspto-grants-2015_09
Patent number
US09139585B2

Reaction notes

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