1,1-Dimethylethyl N-(5-ethynyl-2,2-dimethyl-1,3-dioxan-5-yl)carbamate → Tert-butyl 5-(5-(5-(3-chloro-4-propoxy phenyl)-1,2,4-oxadiazol-3-yl)benzofuran-2-yl)-2,2-dimethyl-1,3-dioxan-5-ylcarbamate

HRID 2046098Notes

Reaction equation

HRID 2046098 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[C:19](I)[CH:18]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][CH3:11].[C:25]([C:27]1([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:32][O:31][C:30]([CH3:34])([CH3:33])[O:29][CH2:28]1)#[CH:26]>CN(C=O)C.CCN(C(C)C)C(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]4[O:23][C:25]([C:27]5([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:32][O:31][C:30]([CH3:34])([CH3:33])[O:29][CH2:28]5)=[CH:26][C:19]=4[CH:18]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][CH3:11]

Participants

5

Reactant 2

HCID 115143851,1-Dimethylethyl N-(5-ethynyl-2,2-dimethyl-1,3-dioxan-5-yl)carbamateHCID 1363599364-(5-(3-Chloro-4-propoxyphenyl)-1,2,4-oxadiazol-3-yl)-2-iodophenol

Product 1

HCID 66614932Tert-butyl 5-(5-(5-(3-chloro-4-propoxy phenyl)-1,2,4-oxadiazol-3-yl)benzofuran-2-yl)-2,2-dimethyl-1,3-dioxan-5-ylcarbamateYield 85.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Conditions

Temperature
45 °C

Procedure

A solution of the product of Step C (0.1 g; 0.22 mmol) and tert-butyl 5-ethynyl-2,2-dimethyl-1,3-dioxan-5-ylcarbamate (0.056 g; 0.22 mmol) in a mixture of DMF and DIPEA (3 ml: 0.3 ml) was degassed with N2 and Cl2Pd(PPh3)4 (0.025 g) was added, followed by catalytic amount of CuI. The mixture was stirred overnight at 45° C. under N2, diluted to 20 ml with saturated NH4Cl and extracted with EtOAc (40 ml). The organic layer was separated, dried over MgSO4 and filtered. The filtrate was distilled off and the residue was purified by FCC (SiO2, hexane/EtOAc) to give the title compound (0.11 g, 78%), as pale paste. 1H-NMR (CDCl3) 8.34 (d, 1H, J=1.29 Hz); 8.24 (d, 1H, J=2.13 Hz); 8.08 (t, 1H, J=1.56 Hz); 8.05 (t, 1H, J=1.56 Hz); 7.53 (d, 1H, J=8.67 Hz); 7.03 (d, 1H, J=8.67 Hz); 6.75 (s, 1H); 4.26-4.19 (m, 4H); 4.06 (t, 2H, J=5.49 Hz); 1.94-1.87 (m, 2H); 1.41 (s, 9H); 1.36 (s, 6H); 1.1 (t, 3H, J=7.44 Hz).

Workup

  1. customwas degassed with N2 and Cl2Pd(PPh3)4 (0.025 g)
  2. additionwas added
  3. additiondiluted to 20 ml with saturated NH4Cl
  4. extractionextracted with EtOAc (40 ml)
  5. customThe organic layer was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. distillationThe filtrate was distilled off
  9. customthe residue was purified by FCC (SiO2, hexane/EtOAc)

Sources & evidence

ORD record
ord-55a1961eb2964aaf876e5e06ca2e3793
Source dataset
uspto-grants-2013_11
Patent number
US08592399B2

Reaction notes

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