Sodium Carbonate → HCID 86728182, compound

HRID 1771101Notes

Reaction equation

HRID 1771101 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][CH2:11][CH:12]([NH2:14])[CH3:13])[CH:5]=[CH:6][C:7]=1[Cl:8].C(=O)([O-])[O-].[Na+].[Na+].Cl[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][CH2:11][CH:12]([NH:14][C:22](=[O:23])[O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH3:13])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 64503636HCID 64503636, compound

Product 1

HCID 86728182HCID 86728182, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Intermediate 18A (0.500 g, 2.15 mmol) and sodium carbonate (0.50 g, 4.7 mmol) were combined in THF (10 mL) and treated with benzyl chloroformate (0.31 mL, 2.2 mmol) drop wise over 15 min. The reaction mixture was stirred at rt for 18 h. The mixture was concentrated in vacuo, diluted with DCM and washed with saturated Na2CO3 twice, brine and the organic portion dried over Na2SO4, filtered and concentrated. The residue was purified by ISCO chromatography (EtOAc/Hexanes 0-50%, column 40 g) to give benzyl 5-(3,4-dichlorophenyl)pentan-2-ylcarbamate (440 mg, 1.20 mmol, 56.0%) as a clear oil. HPLC/MS (HPLC Method L): RT=2.32 min, [M+1]+ =366.0. The racemates were separated on chiral prep HPLC (chiral AD 10 micron 4.6×250 mm, 15 min 5% isocratic. A=EtOH/MeOH (50/50). B=Heptane; retention time=9.8 min) to afford Intermediate 18B (220 mg, 0.600 mmol, 28.0%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.07 (3H, d), 1.32-1.41 (2H, m), 1.51-1.62 (2H, m), 2.42-2.57 (2H, m), 3.62-3.75 (1H, m), 4.42 (1H, br. s.), 5.02 (2H, s), 6.91 (1H, d, J=7.5 Hz), 7.17 (1H, br. s.), 7.23-7.31 (6H, m).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additiondiluted with DCM
  3. washwashed with saturated Na2CO3 twice
  4. dry with materialbrine and the organic portion dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by ISCO chromatography (EtOAc/Hexanes 0-50%, column 40 g)

Sources & evidence

ORD record
ord-03c7c5795c74475c9cb0eb3ceb3be1a7
Source dataset
uspto-grants-2016_02
Patent number
US09249096B2

Reaction notes

Loading…