Methanol → HCID 178497119, compound

HRID 2360934Notes

Reaction equation

HRID 2360934 reaction equation
FC(F)(F)S([N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]([N:17]3[CH2:22][CH2:21][CH2:20][C@@H:19]4[C:23]5[CH:24]=[C:25](OS(C(F)(F)F)(=O)=O)[CH:26]=[CH:27][C:28]=5[CH2:29][C@H:18]34)=[O:16])=[CH:14][C:9]=2[N:8]=[CH:7]1)(=O)=O.N1C2C=CC=CC=2NC=1.C(N(CC)CC)C.CN(C)[CH:58]=[O:59].[CH3:61][OH:62]>>[CH3:61][O:62][C:58]([C:25]1[CH:26]=[CH:27][C:28]2[CH2:29][C@H:18]3[C@@H:19]([C:23]=2[CH:24]=1)[CH2:20][CH2:21][CH2:22][N:17]3[C:15]([C:13]1[CH:12]=[CH:11][C:10]2[NH:6][CH:7]=[N:8][C:9]=2[CH:14]=1)=[O:16])=[O:59]

Participants

6

Reactant 5

HCID 887MethanolHCID 5798BenzimidazoleHCID 6228DimethylformamideHCID 8471TriethylamineHCID 86654157HCID 86654157, compound

Product 1

HCID 178497119HCID 178497119, compound

Conditions

Temperature
70 °C

Procedure

A flask charged with a stir bar, trifluoromethanesulfonic acid cis-1-(1-trifluoromethane-sulfonyl-1H-benzoimidazole-5-carbonyl)-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridin-6-yl ester (mixture of isomers regarding sulfonyl group attachment to N-1 or N-3 of the benzimidazole, 0.50 g), triethylamine (0.18 mL), N,N-dimethylformamide (2 mL), and methanol (1 ml) is sparged with argon for 5 min. [1,1′-Bis(diphenylphosphino)ferrocene]-dichloropalladium dichloromethane complex (53 mg) is added and the mixture is sparged with carbon monoxide for another 5 min. The mixture is then heated to 70° C. under carbon monoxide atmosphere (4 bar) and shaken at this temperature overnight. After cooling to room temperature, the mixture is filtered and the filtrate is concentrated under reduced pressure. The residue is chromatographed on silica gel (dichloromethane/methanol 1:0→9:1) to afford the title compound. Yield: 0.27 g (87% of theory); LC (method 1): tR=2.43 min; Mass spectrum (ESI+): m/z=376 [M+H]+.

Workup

  1. additionA flask charged with a stir bar
  2. customis sparged with argon for 5 min. [1,1′-Bis(diphenylphosphino)ferrocene]-dichloropalladium dichloromethane complex (53 mg)
  3. additionis added
  4. customthe mixture is sparged with carbon monoxide for another 5 min
  5. temperatureAfter cooling to room temperature
  6. filtrationthe mixture is filtered
  7. concentrationthe filtrate is concentrated under reduced pressure
  8. customThe residue is chromatographed on silica gel (dichloromethane/methanol 1:0→9:1)

Sources & evidence

ORD record
ord-5658ad11d1024beda561e0e40b4db2c5
Source dataset
uspto-grants-2014_04
Patent number
US08686149B2

Reaction notes

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