Diisopropylethylamine → HCID 178459587, compound

HRID 2207262Notes

Reaction equation

HRID 2207262 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([OH:13])=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH2:47]([O:50][C:51]([C@H:53]1[CH2:58][CH2:57][C@H:56]([CH:59]([NH:62][C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[CH2:60][NH2:61])[CH2:55][CH2:54]1)=[O:52])[CH2:48][CH3:49]>CN(C=O)C>[CH2:47]([O:50][C:51]([C@H:53]1[CH2:58][CH2:57][C@H:56]([CH:59]([NH:62][C:63]([O:65][C:66]([CH3:67])([CH3:69])[CH3:68])=[O:64])[CH2:60][NH:61][C:11]([C:8]2([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[CH2:9][CH2:10]2)=[O:13])[CH2:55][CH2:54]1)=[O:52])[CH2:48][CH3:49]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 986061-(p-Chlorophenyl)cyclopropanecarboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178459588HCID 178459588, compound

Product 1

HCID 178459587HCID 178459587, compoundYield 92.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

1-(4-Chlorophenyl)cyclopropanecarboxylic acid (527 mg, 2.68 mmol, 1.0 eq) was dissolved in anhydrous DMF (20 mL) in a 250 mL RB flask, under argon. HBTU (1.32 g, 3.48 mmol, 1.3 eq), and DIPEA (0.95 mL, 5.36 mmol, 2.0 eq) were added to this solution. The reaction mixture was stirred at RT for 15 minutes. To this mixture was charged cis-/trans-4-(2-Amino-1-tert-butoxycarbonylamino-ethyl)-cyclohexanecarboxylic acid propyl ester (1-7) (880 mg, 2.68 mmol, 1.0 eq) in anhydrous DMF (20 mL) solution. The reaction mixture was stirred at RT for 2 hours. LC/MS indicated the absence of the starting material. DMF was removed under vacuum. The residue was treated with 1:1 brine/EtOAc (300 mL). The aqueous layer was extracted with EtOAc (2×150 mL). The combined EtOAc extracts were washed with brine (1×150 mL), dried over Na2SO4 and the solvent evaporated to dryness. The crude product was purified on a silica gel column, eluting with EtOAc/Hexanes (20˜25%) to give 1.26 g (92% yield) of 1-9. The 1H NMR (DMSO-d6) data is depicted in FIG. 6.

Workup

  1. stirringThe reaction mixture was stirred at RT for 2 hours
  2. customDMF was removed under vacuum
  3. additionThe residue was treated with 1:1 brine/EtOAc (300 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (2×150 mL)
  5. washThe combined EtOAc extracts were washed with brine (1×150 mL)
  6. dry with materialdried over Na2SO4
  7. customthe solvent evaporated to dryness
  8. customThe crude product was purified on a silica gel column
  9. washeluting with EtOAc/Hexanes (20˜25%)

Sources & evidence

ORD record
ord-e9ab8cf6630049c2b05500162c38fa54
Source dataset
uspto-grants-2016_06
Patent number
US09376423B2

Reaction notes

Loading…