Methanol → 2-(4-chloro-3-(hydroxymethyl)pyridin-2-yl)-7,7-dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one

HRID 1411781Notes

Reaction equation

HRID 1411781 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:19][CH2:18][N:17]3[C:10](=[CH:11][C:12]4[CH2:13][C:14]([CH3:21])([CH3:20])[CH2:15][C:16]=43)[C:9]2=[O:22])[C:3]=1[CH:23]=[O:24].CO.[BH4-].[Na+]>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:19][CH2:18][N:17]3[C:10](=[CH:11][C:12]4[CH2:13][C:14]([CH3:21])([CH3:20])[CH2:15][C:16]=43)[C:9]2=[O:22])[C:3]=1[CH2:23][OH:24]

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 768540784-chloro-2-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta(4,5)pyrrolo(1,2-a)pyrazin-2-yl)nicotinaldehyde

Product 1

HCID 866843692-(4-chloro-3-(hydroxymethyl)pyridin-2-yl)-7,7-dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-oneYield 77.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with 4-chloro-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-3-carbaldehyde 108a (9.0 g, 26.1 mmol, 1.0 eq.), methanol (50 mL), dichloromethane (30 mL), and NaBH4 (5.95 g, 156.6 mmol, 5.0 eq.) at 0° C. The reaction mixture was stirred for 1 h. After the reaction was completed, the reaction was quenched with water and concentrated under reduced pressure. The residue was extracted with dichloromethane. The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:4 ethyl acetate/petroleum ether to afford 199c as a white solid (7.0 g, 77%). MS-ESI: [M+H]+ 345.9.

Workup

  1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. customthe reaction was quenched with water
  3. concentrationconcentrated under reduced pressure
  4. extractionThe residue was extracted with dichloromethane
  5. dry with materialThe combined organic layer was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica-gel column chromatography
  8. washeluting with 1:4 ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-0bf468a617a94665a1748ce4b7d38032
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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