Triethylamine → HCID 58428065, compound

HRID 1473788Notes

Reaction equation

HRID 1473788 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]1[C:10](=[O:26])[N:11]([O:22][CH2:23][O:24][CH3:25])[C:12]2([CH2:19][CH2:18][N:17]([O:20][CH3:21])[CH2:16][CH2:15]2)[C:13]=1[OH:14].C(N(CC)CC)C.[CH:34]1([C:37](Cl)=[O:38])[CH2:36][CH2:35]1>CN(C)C1C=CN=CC=1.O1CCCC1>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]1[C:10](=[O:26])[N:11]([O:22][CH2:23][O:24][CH3:25])[C:12]2([CH2:15][CH2:16][N:17]([O:20][CH3:21])[CH2:18][CH2:19]2)[C:13]=1[O:14][C:37]([CH:34]1[CH2:36][CH2:35]1)=[O:38]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 58427975HCID 58427975, compound

Product 1

HCID 58428065HCID 58428065, compoundYield 84.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-(2,5-dimethyl-phenyl)-4-hydroxy-8-methoxy-1-methoxymethoxy-1,8-diaza-spiro[4.5]dec-3-en-2-one (compound P2ii.2) (200 mg, 0.55 mmol), triethylamine (0.153 ml, 111 mg, 1.10 mmol) and a catalytic amount of 4-dimethylaminopyridine in tetrahydrofuran (6 ml) at 0° C. was added cyclopropanecarboxylic acid chloride (0.066 ml, 75 mg, 0.72 mmol) dropwise. The suspension was stirred at 0° C. for 10 minutes, and at room temperature for one hour. The reaction mixture was evaporated, diluted with ethyl acetate and filtered to remove salts. The filtrate was washed with a saturated aqueous sodium hydrogen carbonate solution and brine, dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (ethyl acetate/hexane 1:2) to afford 200 mg of an oily product. This material was triturated with diethyl ether, filtered and dried. Yield: 190 mg of cyclopropanecarboxylic acid 3-(2,5-dimethyl-phenyl)-8-methoxy-1-methoxymethoxy-2-oxo-1,8-diaza-spiro[4.5]dec-3-en-4-yl ester (title compound P1ii.4) as a white solid, mp 114-116° C.

Workup

  1. waitat room temperature for one hour
  2. customThe reaction mixture was evaporated
  3. additiondiluted with ethyl acetate
  4. filtrationfiltered
  5. customto remove salts
  6. washThe filtrate was washed with a saturated aqueous sodium hydrogen carbonate solution and brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (ethyl acetate/hexane 1:2)

Sources & evidence

ORD record
ord-9abd069f183b4573b2b443180b34bdb4
Source dataset
uspto-grants-2015_04
Patent number
US09018135B2

Reaction notes

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