N-iodoacetyl-3,5-dimethyl piperidine → (R)-1-{9-[2-(3,5-Dimethylpiperidin-1-yl)-2-oxo-ethyl]-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl}-3-m-tolyl-urea

HRID 53126Notes

Reaction equation

HRID 53126 reaction equation
[O:1]=[C:2]1[NH:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[O:5][CH2:4][C@H:3]1[NH:13][C:14]([NH:16][C:17]1[CH:18]=[C:19]([CH3:23])[CH:20]=[CH:21][CH:22]=1)=[O:15].I[CH2:25][C:26]([N:28]1[CH2:33][CH:32]([CH3:34])[CH2:31][CH:30]([CH3:35])[CH2:29]1)=[O:27]>C1COCC1>[CH3:35][CH:30]1[CH2:31][CH:32]([CH3:34])[CH2:33][N:28]([C:26](=[O:27])[CH2:25][N:8]2[C:7]3[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=3[O:5][CH2:4][C@@H:3]([NH:13][C:14]([NH:16][C:17]3[CH:18]=[C:19]([CH3:23])[CH:20]=[CH:21][CH:22]=3)=[O:15])[C:2]2=[O:1])[CH2:29]1

Participants

4

Reactant 2

HCID 19961717N-iodoacetyl-3,5-dimethyl piperidineHCID 54538732(R)-(8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)-3-m-tolyl-urea

Product 1

HCID 67721511(R)-1-{9-[2-(3,5-Dimethylpiperidin-1-yl)-2-oxo-ethyl]-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl}-3-m-tolyl-ureaYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.100 g (0.000325M) (R)-(8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)-3-m-tolyl-urea in 5 ml of THF was cooled to -78° C. under a nitrogen atmosphere. To this solution was added dropwise 0.321 mL (0.000325M) of lithium bis-hexamethyldisilylamide (1M solution in THF) and the reaction was stirred for 15 minutes. To this mixture was added 0.090 ml (0.000325M) of N-iodoacetyl-3,5-dimethyl piperidine. After addition was complete, the reaction was warmed to room temperature and stirred for 30 minutes. The reaction mixture was quenched with 5 mL of water, and extracted with ethyl acetate. The ethyl acetate extracts were dried and evaporated. The residue was chromatographed on 15 g of silica using 10:1 chloroform:methanol as the eluant. The appropriate fractions were combined and evaporated to yield 109 mg (72% yield) of product as a white solid.

Workup

  1. additionAfter addition
  2. stirringstirred for 30 minutes
  3. customThe reaction mixture was quenched with 5 mL of water
  4. extractionextracted with ethyl acetate
  5. dry with materialThe ethyl acetate extracts were dried
  6. customevaporated
  7. customThe residue was chromatographed on 15 g of silica using 10:1 chloroform
  8. customevaporated

Sources & evidence

ORD record
ord-c597b4ebf2a84e8e9d8c832831e0c48f
Source dataset
uspto-grants-1997_04
Patent number
US05618808

Reaction notes

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