Methyl chloroformate → HCID 86680526, compound

HRID 1184611Notes

Reaction equation

HRID 1184611 reaction equation
[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:40][N:14]4[CH2:15][CH2:16][N:17]([C:19](=[O:39])[CH:20]([NH:31][C:32](=[O:38])[O:33][C:34](C)(C)C)[C:21]5[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=5)[CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.ClC(OC)=O.C(N(CC)CC)C>O1CCOCC1.Cl>[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:40][N:14]4[CH2:15][CH2:16][N:17]([C:19](=[O:39])[CH:20]([NH:31][C:32](=[O:38])[O:33][CH3:34])[C:21]5[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:28])[F:29])[CH:22]=5)[CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 86680527HCID 86680527, compound

Product 1

HCID 86680526HCID 86680526, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A solution of the product from Example 180 (50 mg, 0.089 mmol) in 1,4-dioxane (0.5 mL) and 4 N HCl in 1,4-dioxane (0.5 mL, 2.00 mmol) was stirred at room temperature for 90 minutes and then concentrated in vacuo. Dichloromethane (1 mL) was added to the residue, followed by methyl chloroformate (7.6 μL, 0.098 mmol) and triethylamine (0.062 mL, 0.445 mmol). The resulting solution was stirred at room temperature for 90 minutes. The mixture was partitioned between water and dichloromethane (3×), and the combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-10% methanol in dichloromethane. The title compound was obtained as a semi-solid (18 mg, 39%). 1H NMR (300 MHz, CDCl3) δ ppm 0.82-1.02 (m, 4 H) 1.18-3.31 (m, 9 H) 3.50-3.89 (m, 5 H) 4.54-4.82 (m, 1 H) 5.17-5.38 (m, 1 H) 5.56-5.72 (m, 1 H) 6.25-6.41 (m, 1 H) 7.40-7.69 (m, 4 H) 7.85-8.05 (m, 2 H); MS (ESI) m/z 520 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. additionDichloromethane (1 mL) was added to the residue
  3. customThe mixture was partitioned between water and dichloromethane (3×)
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-135e6481bf2e45588c0221e452d80054
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

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