Dichloromethane → 1,1-Dimethylethyl(3s-trans)-4-[[[(8-chloro-3,4-dihydro-2h-1,5-benzodioxepin6-yl)carbonyl]amino]methyl]-3-hydroxy-1-piperidinecarboxylate monohydrate

HRID 1264653Notes

Reaction equation

HRID 1264653 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:13]([OH:15])=O)[C:5]2[O:11][CH2:10][CH2:9][CH2:8][O:7][C:6]=2[CH:12]=1.C(Cl)Cl.ClC(OCC)=O.[NH2:25][CH2:26][C@@H:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][C@H:28]1[OH:40]>C(N(CC)CC)C>[OH2:7].[Cl:1][C:2]1[CH:3]=[C:4]([C:13]([NH:25][CH2:26][C@@H:27]2[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:38])([CH3:37])[CH3:39])=[O:34])[CH2:29][C@H:28]2[OH:40])=[O:15])[C:5]2[O:11][CH2:10][CH2:9][CH2:8][O:7][C:6]=2[CH:12]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10928Ethyl chloroformateHCID 11075229trans-1-Boc-4-aminomethyl-3-hydroxypiperidineHCID 112299388-chloro-3,4-dihydro-2H-1,5-benzodioxepin-6-carboxylic acid

Product 1

HCID 205757661,1-Dimethylethyl(3s-trans)-4-[[[(8-chloro-3,4-dihydro-2h-1,5-benzodioxepin6-yl)carbonyl]amino]methyl]-3-hydroxy-1-piperidinecarboxylate monohydrateYield 191.7%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent2×

Procedure

Intermediate (11) (0.1 mol), triethylamine (0.1 mol) and DCM (500 ml) were stirred at a temperature below 10° C. Ethyl chloroformate (0.1 mol) was added dropwise at temperature below 10° C. The mixture was stirred for 30 minutes at a temperature below 10° C. A solution of 1,1-dimethylethyl (3S-trans)-4-(aminomethyl)-3-hydroxy-1-piperidinecarboxylate (0.1 mol) in triethylamine (250 ml) was added at a temperature below 10° C. The reaction mixture was stirred for one hour at room temperature. The mixture was concentrated to half the initial volume. The concentrate was washed with water, with H2O/50% NaOH, and again with water. The organic layer was separated, dried, filtered and the solvent was evaporated, yielding 44 g of 1,1-dimethylethyl(3S-trans)-4-[[[(8-chloro-3,4-dihydro-2H-1,5-benzodioxepin6-yl)carbonyl]amino]methyl]-3-hydroxy-1-piperidinecarboxylate monohydrate (intermediate 12) (mp: 88° C.; sticky) [α]D20=−0.97° (c=25.71 mg/5 ml in CH3OH).

Workup

  1. stirringThe reaction mixture was stirred for one hour at room temperature
  2. concentrationThe mixture was concentrated to half the initial volume
  3. washThe concentrate was washed with water, with H2O/50% NaOH
  4. customThe organic layer was separated
  5. customdried
  6. filtrationfiltered
  7. customthe solvent was evaporated

Sources & evidence

ORD record
ord-a79f497e52ec48edb574640fc97bad90
Source dataset
uspto-grants-2003_04
Patent number
US06544997B1

Reaction notes

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