1,2-Dichloroethane → N-t-Butoxycarbonyl-5-[(morpholin-4-yl)carbonyl]isoindoline

HRID 268716Notes

Reaction equation

HRID 268716 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:17]([OH:19])=O)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C(N(CC)CC)C.[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1>C(Cl)Cl.C1C=NC2N(O)N=NC=2C=1>[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:17]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[O:19])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 8083MorpholineHCID 8471TriethylamineHCID 164501432-(tert-Butoxycarbonyl)-2,3-dihydro-1H-isoindole-5-carboxylic acid

Product 1

HCID 17986287N-t-Butoxycarbonyl-5-[(morpholin-4-yl)carbonyl]isoindoline

Reagents, catalysts & solvents 2

HCID 181649HOAtCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of N-t-butoxycarbonyl-5-carboxyisoindoline (D13) (300 mg), EDC (440 mg), HOAT (10 mg), triethylamine (0.4 ml) and morpholine (0.12 ml) in DCM (10 ml) was stirred overnight and then evaporated. The residue was redissolved in EtOAc (10 ml), washed with saturated NaHCO3 solution (10 ml), water (10 ml), brine (10 ml), dried (MgSO4) and evaporated. The residue was chromatographed on a silica gel flash column [step gradient 70-90% EtOAc in light petroleum 40-60] to give the title compound (D19) (314 mg). MS electrospray (+ion) 333 (MH+). 1H NMR δ (CDCl3): 7.30 (3H, m), 4.70 (2H, m), 4.67 (2H, m), 3.70 (8H, m), 1.52 (9H, s).

Workup

  1. customevaporated
  2. dissolutionThe residue was redissolved in EtOAc (10 ml)
  3. washwashed with saturated NaHCO3 solution (10 ml), water (10 ml), brine (10 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was chromatographed on a silica gel flash column [step gradient 70-90% EtOAc in light petroleum 40-60]

Sources & evidence

ORD record
ord-117746c291fb4161a0b17860b2855f4e
Source dataset
uspto-grants-2008_11
Patent number
US07446103B2

Reaction notes

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