Isobutyl chloroformate → HCID 11155195, compound

HRID 1833272Notes

Reaction equation

HRID 1833272 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9]([C:15](=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=1)=[N:8][CH:7]=[C:6]2[C:25]([OH:27])=O.C(OC(Cl)=O)C(C)C.Cl.[CH2:37]([O:39][C:40](=[O:43])[CH2:41][NH2:42])[CH3:38]>CN(C)C=O.C(N(CC)CC)C.C(OCC)(=O)C>[CH2:37]([O:39][C:40](=[O:43])[CH2:41][NH:42][C:25]([C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[C:9]([C:15](=[O:24])[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=2)=[N:8][CH:7]=1)=[O:27])[CH3:38]

Participants

7

Reactant 3

HCID 62365Isobutyl chloroformateHCID 2723640Glycine ethyl ester, hydrochlorideHCID 11394498HCID 11394498, compound

Product 1

HCID 11155195HCID 11155195, compoundYield 6.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 6,7-dimethoxy-1-(3-methoxy-benzoyl)-isoquinoline-4-carboxylic acid (30.0 mg, 81.65 mmol) in dry, N,N-dimethylformamide (2 mL) chilled in an ice-bath under argon. With stirring, triethylamine (14.4 uL, 102 mmol) and isobutylchloroformate (13.4 uL, 102 mmol) were added. The solution was stirred for 30 min and then solution of glycine ethyl ester hydrochloride (227 mg, 1,633 mM) in 4 mL of dimethylformamide and triethylamine (0.229 mL, 1.633 mM) were added and the reaction was allowed to warm to room temperature with stirring for 1 hr. and then diluted with ethyl acetate (30 mL), The ethyl acetate solution was washed sequentially with saturated sodium bicarbonate solution (2×5 mL), water (5 mL), and saturated sodium chloride solution (5 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to afford 46 mg solid. This crude material was purified by flash chromatography, eluting with 50% ethyl acetate in hexanes (containing 1% acetic acid) and then increasing gradually to 80% ethyl acetate in hexanes After tlc analysis, fractions were pooled and evaporated to yield 36 mg (79.4%) of white, powder as an acetate salt: APCI-MS m/e calcd for C24H24N2O7 (M+H) 453.5, found 453; H NMR (300 MHz) compatible

Workup

  1. stirringThe solution was stirred for 30 min
  2. stirringwith stirring for 1 hr
  3. washThe ethyl acetate solution was washed sequentially with saturated sodium bicarbonate solution (2×5 mL), water (5 mL), and saturated sodium chloride solution (5 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d0028e7035f94d3b8c70da64ed61ddc0
Source dataset
uspto-grants-2006_06
Patent number
US07067529B2

Reaction notes

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