Rac-(1r,4r)-4-methoxycyclohexane-1-carboxylic acid → 1-(Methylcarbonyloxy-methyl)-5-(4-methoxy-cyclohexyl-cabonyl)-spiro[indoline-3,4'-piperidin]-2-one

HRID 1441678Notes

Reaction equation

HRID 1441678 reaction equation
[CH3:1][O:2][CH:3]1[CH2:8][CH2:7][CH:6]([C:9]([OH:11])=O)[CH2:5][CH2:4]1.Cl.CN(C)CCCN=C=N[CH2:21][CH3:22].[OH2:24].[OH:25]N1C2C=CC=CC=2N=N1.COC([CH2:39][N:40]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:42]2([CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)[C:41]1=[O:54])=O>ClCCl.CN(C)C=O>[CH3:22][C:21]([O:25][CH2:39][N:40]1[C:53]2[C:48](=[CH:49][C:50]([C:9]([CH:6]3[CH2:5][CH2:4][CH:3]([O:2][CH3:1])[CH2:8][CH2:7]3)=[O:11])=[CH:51][CH:52]=2)[C:42]2([CH2:43][CH2:44][NH:45][CH2:46][CH2:47]2)[C:41]1=[O:54])=[O:24]

Participants

7

Reactant 4

HCID 736153Rac-(1r,4r)-4-methoxycyclohexane-1-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 591645371-(Methoxycarbonylmethyl)-spiro[indoline-3,4'-piperidin]-2-one

Product 1

HCID 685703611-(Methylcarbonyloxy-methyl)-5-(4-methoxy-cyclohexyl-cabonyl)-spiro[indoline-3,4'-piperidin]-2-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

4-Methoxy-cyclohexanecarboxylic acid (0.006 g, 0.036 mmol) was suspended in dry dichloromethane (1 mL) and dry N,N-dimethylformamide (0.05 mL). 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl salt (0.005 g, 0.04 mmol) and 1-hydroxybenzotriazole hydrate (0.006 g, 0.047 mmol) were added and the reaction mixture was stirred under nitrogen atmosphere at room temperature for 30 minutes. A solution of 1-(methoxycarbonyl-methyl)-spiro[indoline-3,4′-piperidin]-2-one (0.010 g, 0.036 mmol) in dry dichloromethane (1 mL) was added under nitrogen atmosphere and the reaction mixture was stirred under nitrogen atmosphere at room temperature for 18 hrs. The reaction mixture was then partitioned with water and dichloromethane. The organic layer was washed with aqueous NaHCO3, aqueous 0.5 N HCl, brine, dried with Na2SO4, filtered and the solvent evaporated in vacuo to yield a crude oil. The crude oil was purified via flash chromatography (4% ammonia 2.0 M in methanol/dichloromethane) to yield the title compound as an oil.

Workup

  1. stirringthe reaction mixture was stirred under nitrogen atmosphere at room temperature for 18 hrs
  2. customThe reaction mixture was then partitioned with water and dichloromethane
  3. washThe organic layer was washed with aqueous NaHCO3, aqueous 0.5 N HCl, brine
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. customthe solvent evaporated in vacuo
  7. customto yield a crude oil
  8. customThe crude oil was purified via flash chromatography (4% ammonia 2.0 M in methanol/dichloromethane)

Sources & evidence

ORD record
ord-0e4f1dc9964a4678b12179e0d5bfe4d3
Source dataset
uspto-grants-2010_02
Patent number
US07655670B2

Reaction notes

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