Sodium Carbonate → (+/-)-Tert-butyl 1-[3-({[4-(acetoxymethyl)phenyl](cyclopentyl)acetyl}-amino)benzyl]cyclopropanecarboxylate

HRID 1475653Notes

Reaction equation

HRID 1475653 reaction equation
[C:1]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:13]([OH:15])=O)=[CH:8][CH:7]=1)(=[O:3])[CH3:2].O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH2:41][C:42]1[CH:43]=[C:44]([CH:56]=[CH:57][CH:58]=1)[CH2:45][C:46]1([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:48][CH2:47]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[C:1]([O:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]([CH:12]([CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:13]([NH:41][C:42]2[CH:43]=[C:44]([CH:56]=[CH:57][CH:58]=2)[CH2:45][C:46]2([C:49]([O:51][C:52]([CH3:55])([CH3:53])[CH3:54])=[O:50])[CH2:48][CH2:47]2)=[O:15])=[CH:10][CH:11]=1)(=[O:3])[CH3:2]

Participants

8

Reactant 6

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58136423[4-(Acetoxymethyl)phenyl](cyclopentyl)acetic acidHCID 58136514tert-Butyl 1-(3-aminobenzyl)cyclopropanecarboxylate

Product 1

HCID 68170303(+/-)-Tert-butyl 1-[3-({[4-(acetoxymethyl)phenyl](cyclopentyl)acetyl}-amino)benzyl]cyclopropanecarboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

9.50 g (34.4 mmol) of (+/−)-[4-(acetoxymethyl)phenyl](cyclopentyl)acetic acid were dissolved in 67.5 ml of DMF, and 5.58 g (41.25 mmol) of 1-hydroxy-1H-benzotriazole hydrate (HOBt) were added. The mixture was cooled to 0° C., and 15.0 ml (85.95 mmol) of N,N-diisopropylethylamine and 10.63 g (42.97 mmol) of tert-butyl 1-(3-aminobenzyl)cyclopropanecarboxylate, dissolved in a little DMF, were added. 14.38 g (37.82 mmol) of HATU were then added in several portions, and the reaction mixture was slowly warmed to RT and then stirred overnight. The mixture was then added to saturated aqueous sodium carbonate solution. After phase separation, the aqueous phase was extracted repeatedly with ethyl acetate, and the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase dichloromethane/ethyl acetate 50:1→20:1). This gave 12.86 g of the target compound (69.4% of theory).

Workup

  1. additionwere added
  2. temperaturethe reaction mixture was slowly warmed to RT
  3. customAfter phase separation
  4. extractionthe aqueous phase was extracted repeatedly with ethyl acetate
  5. washthe combined organic phases were washed with saturated sodium chloride solution
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by chromatography on silica gel (mobile phase dichloromethane/ethyl acetate 50:1→20:1)

Sources & evidence

ORD record
ord-c5058435428945b6bd62037aedc20f94
Source dataset
uspto-grants-2015_04
Patent number
US09018258B2

Reaction notes

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