Dimethylformamide → (R)-1-(2-chlorobutanoyl)-3,3-dimethylindoline-6-carbonitrile

HRID 1475533Notes

Reaction equation

HRID 1475533 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N([CH2:30][CH3:31])CC)C.[CH3:32][C:33]1([CH3:44])[C:41]2[C:36](=[CH:37][C:38]([C:42]#[N:43])=[CH:39][CH:40]=2)[NH:35][CH2:34]1.CN([CH:48]=[O:49])C.[CH2:50](Cl)[Cl:51]>C(OCC)(=O)C>[Cl:51][C@H:50]([CH2:30][CH3:31])[C:48]([N:35]1[C:36]2[C:41](=[CH:40][CH:39]=[C:38]([C:42]#[N:43])[CH:37]=2)[C:33]([CH3:44])([CH3:32])[CH2:34]1)=[O:49]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 107023412,3-dihydro-3,3-dimethyl-1H-indole-6-carbonitrile

Product 1

HCID 86724047(R)-1-(2-chlorobutanoyl)-3,3-dimethylindoline-6-carbonitrile

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (R)-2-chloro-1-butyric acid (0.47 mL, 4.60 mmol) in DCM was added HBTU (2.18 g, 5.75 mmol). After stirring for 30 min, triethylamine (0.96 mL, 6.9 mmol) and 3,3-dimethyl-2,3-dihydro-1H-indole-6-carbonitrile (0.80 g, 4.6 mmol) were added, the resulting mixture was stirred overnight. A drop of DMF was added and the reaction was stirred overnight. The reaction mixture was then diluted with ethyl acetate and washed with water. The organics were separated, dried with sodium sulfate and concentrated. The residue was purified by flash column chromatography on silica gel eluting with 20% ethyl acetate in heptane to give (R)-1-(2-chlorobutanoyl)-3,3-dimethylindoline-6-carbonitrile containing un-reacted 3,3-dimethyl-2,3-dihydro-1H-indole-6-carbonitrile. The mixture was taken up in DCM and washed with 2M HCl solution. The organics were dried with sodium sulfate and concentrated, to give (R)-1-(2-chlorobutanoyl)-3,3-dimethylindoline-6-carbonitrile (0.38 g). 1H NMR (400 MHz, CDCl3) 8.53 (s, 1H), 7.38 (d, 1H), 7.25 (d, 1H), 4.22-4.29 (m, 1H), 4.15 (d, 1H), 3.87 (d, 1H), 2.19-2.04 (m, 2H), 1.39 (s, 6H), 1.09 (t, 3H).

Workup

  1. stirringthe resulting mixture was stirred overnight
  2. stirringthe reaction was stirred overnight
  3. washwashed with water
  4. customThe organics were separated
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography on silica gel eluting with 20% ethyl acetate in heptane

Sources & evidence

ORD record
ord-6a19a84b793849aaa07f33d99a3af3b4
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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