Dimethylacetamide → (S)-(7-Cyano-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbamic Acid Isopropyl Ester

HRID 1928579Notes

Reaction equation

HRID 1928579 reaction equation
[CH:1]([O:4][C:5](=[O:20])[NH:6][C@@H:7]1[CH2:19][C:10]2[NH:11][C:12]3[CH:13]=[CH:14][C:15](Br)=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2].C[C:22]([N:24](C)C)=O>[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C([O-])=O.[Zn+2].C([O-])=O>[CH:1]([O:4][C:5](=[O:20])[NH:6][C@@H:7]1[CH2:19][C:10]2[NH:11][C:12]3[CH:13]=[CH:14][C:15]([C:22]#[N:24])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2]

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 45588342propan-2-yl N-[(2S)-7-bromo-1H,2H,3H,4H-cyclopenta[b]indol-2-yl]carbamate

Product 1

HCID 66933207(S)-(7-Cyano-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbamic Acid Isopropyl Ester

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11195Zinc formateCatalystHCID 23938PalladiumCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
110 °C

Procedure

((S)-7-Bromo-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-carbamic acid isopropyl ester (50 g, 148.27 mmol), zinc cyanide (10.45 g, 88.99 mmoles), and palladium (6.31 g, 2.96 mmol) are combined in dimethylacetamide (500 mL). The resulting slurry is sparged with sub-surface nitrogen for 10 min. Then 1,1′-bis(diphenylphosphino)ferrocene (3.29 g, 5.93 mmol) is added and the reaction is sparged for another 10 min. Finally, zinc formate (2.3 g, 14.80 mmol) is added and the reaction is sparged again for 10 min. The reaction is then placed under a nitrogen sweep and heated up to 110° C. overnight. The heat is turned off. The reaction is cooled to 85° C. and 3-mercaptopropyl-functionalized silica gel (5 g, 10 wt %) is added. The mixture is stirred for 2 h while cooling to room temperature. The reaction mixture is then filtered and the solid is rinsed with DMAC (50 mL). To the stirring orange filtrate is added 0.3 M ethylenediaminetetraacetic acid tetrasodium salt in water (1000 mL) over 10 min. The resulting slurry is stirred at room temperature and is filtered. The solid is rinsed with 0.3 M ethylenediaminetetraacetic acid tetrasodium salt (250 mL) followed by water (250 mL). A light brown solid is collected and dried overnight in the vacuum oven to provide the product (42.44 g) in quantitative yield.

Workup

  1. customThe resulting slurry is sparged with sub-surface nitrogen for 10 min
  2. customthe reaction is sparged for another 10 min
  3. customthe reaction is sparged again for 10 min
  4. temperatureThe reaction is cooled to 85° C.
  5. addition3-mercaptopropyl-functionalized silica gel (5 g, 10 wt %) is added
  6. temperaturewhile cooling to room temperature
  7. filtrationThe reaction mixture is then filtered
  8. washthe solid is rinsed with DMAC (50 mL)
  9. additionTo the stirring orange filtrate is added 0.3 M ethylenediaminetetraacetic acid tetrasodium salt in water (1000 mL) over 10 min
  10. stirringThe resulting slurry is stirred at room temperature
  11. filtrationis filtered
  12. washThe solid is rinsed with 0.3 M ethylenediaminetetraacetic acid tetrasodium salt (250 mL)
  13. customA light brown solid is collected
  14. customdried overnight in the vacuum oven

Sources & evidence

ORD record
ord-e46e2a7d24e044ad8dfb8864d0a11ac6
Source dataset
uspto-grants-2012_05
Patent number
US08183388B2

Reaction notes

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