Dimethylformamide → HCID 66933293, compound

HRID 1928577Notes

Reaction equation

HRID 1928577 reaction equation
[C:1]([O:5][C:6](=[O:21])[NH:7][C@@H:8]1[CH2:20][C:11]2[NH:12][C:13]3[CH:14]=[CH:15][C:16](Br)=[CH:17][C:18]=3[C:10]=2[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:22][N:23](C=O)C>[C-]#N.[Zn+2].[C-]#N.C([O-])(=O)C.[Zn+2].C([O-])(=O)C.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].[Pd](Cl)Cl.[Zn]>[C:1]([O:5][C:6](=[O:21])[NH:7][C@@H:8]1[CH2:20][C:11]2[NH:12][C:13]3[CH:14]=[CH:15][C:16]([C:22]#[N:23])=[CH:17][C:18]=3[C:10]=2[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 2

HCID 6228DimethylformamideHCID 66933350HCID 66933350, compound

Product 1

HCID 66933293HCID 66933293, compoundYield 69%

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11192Zinc AcetateCatalystHCID 23994ZincCatalystHCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Procedure

The following reagents are stirred together in DMF (250 mL) at 100° C. for 18 h: ((S)-7-bromo-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-carbamic acid tert-butyl ester (50.0 g, 142 mmol), zinc cyanide (11.9 g, 99.7 mmol), zinc acetate (5.22 g, 28.5 mmol), 1,1′-bis(diphenylphosphino)ferrocene) palladium (II) chloride (Pd(dppf)2Cl2) (1.74 g, 2.14 mmol), and zinc (3.72 g, 56.9 mmol). The reaction is concentrated to dryness and partitioned between water and ethyl acetate. The organics are washed with water and brine, then concentrated to afford a solid. The solid is chromatographed in two equal portions on silica gel (1600 mL) as follows: load as a solution in CH2Cl2 and elute with 2% EtOAc in CH2Cl2 (3 L), then 5% EtOAc in CH2Cl2. The product is recovered from the two columns to give 29 g (69%) of the title compound as a white solid. 1H-NMR (400 MHz, CDCl3) δ 8.39 (s, 1H), 7.74 (s, 1H), 7.34 (d, J=1.8 Hz, 2H), 5.05-4.96 (m, 2H), 3.37-3.25 (m, 2H), 2.80-2.63 (m, 2H), 1.46 (s, 9H).

Workup

  1. concentrationThe reaction is concentrated to dryness
  2. custompartitioned between water and ethyl acetate
  3. washThe organics are washed with water and brine
  4. concentrationconcentrated
  5. customto afford a solid
  6. customThe solid is chromatographed in two equal portions on silica gel (1600 mL)
  7. washload as a solution in CH2Cl2 and elute with 2% EtOAc in CH2Cl2 (3 L)
  8. customThe product is recovered from the two columns

Sources & evidence

ORD record
ord-31f9d24ee3664963b2e5e08cc6ce81f1
Source dataset
uspto-grants-2012_05
Patent number
US08183388B2

Reaction notes

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