Dimethylacetamide → HCID 86682583, compound

HRID 2036216Notes

Reaction equation

HRID 2036216 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][C:15]([F:22])=[C:16]([F:21])[CH:17]=2)[CH:12]1[C:23]1[CH:28]=[C:27](Br)[CH:26]=[CH:25][C:24]=1[O:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:37][N:38](C)C(=O)C>CCOC(C)=O.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.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-]#N.[Zn+2].[C-]#N>[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][C:15]([F:22])=[C:16]([F:21])[CH:17]=2)[CH:12]1[C:23]1[CH:28]=[C:27]([C:37]#[N:38])[CH:26]=[CH:25][C:24]=1[O:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 66654363HCID 66654363, compound

Product 1

HCID 86682583HCID 86682583, compound

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst2×HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst2×HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalyst2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (±)-1-(5-bromo-2-ethoxycarbonylmethoxy-phenyl)-6,7-difluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (126 mg, 0.23 mmol, 1.00 eq.) in N,N-dimethylacetamide (0.45 mL) was added poly(methylhydrosiloxane) (5 μL) at r.t. The reaction mixture was heated to 120° C. and tris(dibenzylideneacetone) dipalladium(0) (4.5 mg, 0.005 mmol, 0.002 eq) then 1,1′-bis-(diphenylphosphino)-ferrocene (3.4 mg, 0.006 mmol, 0.027 eq.) were added. Afterwards, zinc cyanide (6.6 mg, 0.056 mmol, 0.25 eq.) was added. The resulting mixture was stirred at 150° C. during 25 min in a microwave. Zinc cyanide (3.3 mg, 0.028 mmol, 0.13 eq.), tris(dibenzylideneacetone) dipalladium(0) (2.3 mg, 0.002 mmol, 0.001 eq.) and 1,1′-bis-(diphenylphosphino)-ferrocene (1.7 mg, 0.003 mmol, 0.014 eq.) were added again. The resulting mixture was stirred at 150° C. during 25 min in a microwave. The reaction mixture was diluted with AcOEt and filtered over celite. The filtrate was washed with water, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by CC (SiO2, eluent:Hept/AcOEt) to yield the nitrile derivative as a pale yellow oil.

Workup

  1. stirringThe resulting mixture was stirred at 150° C. during 25 min in a microwave
  2. filtrationfiltered over celite
  3. washThe filtrate was washed with water
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by CC (SiO2, eluent:Hept/AcOEt)

Sources & evidence

ORD record
ord-c4d528e2882d4bfeb8ce56dbe7b62eb1
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

Loading…