Ethyl 2-formylcyclopropanecarboxylate → HCID 178468463, compound

HRID 555265

Reaction equation

HRID 555265 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]([N:11]2[CH2:17][C:16]3([CH3:19])[CH2:18][CH:12]2[CH2:13][C:14]([CH3:21])([CH3:20])[CH2:15]3)=[O:10])[CH:5]=[CH:6][C:7]=1[NH2:8].[CH:22]([CH:24]1[CH2:26][CH:25]1[C:27]([O:29][CH2:30][CH3:31])=[O:28])=O>CN1C(=O)CCC1>[CH2:30]([O:29][C:27]([CH:25]1[CH2:26][CH:24]1[C:22]1[NH:8][C:7]2[CH:6]=[CH:5][C:4]([C:9]([N:11]3[CH2:17][C:16]4([CH3:19])[CH2:18][CH:12]3[CH2:13][C:14]([CH3:21])([CH3:20])[CH2:15]4)=[O:10])=[CH:3][C:2]=2[N:1]=1)=[O:28])[CH3:31]

Participants

4

Reactant 2

HCID 89334Ethyl 2-formylcyclopropanecarboxylateHCID 66987132HCID 66987132, compound

Product 1

HCID 178468463HCID 178468463, compoundYield 8.4%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (3,4-diaminophenyl)-(1,3,3-trimethyl-6-azabicyclo[3.2.1]oct-6-yl)methanone (500 mg, 1.74 mmol) in dry NMP (25 mL) at room temperature under an inert atmosphere of nitrogen was added approx. 500 mg of molecular sieve 4 Å followed by ethyl 2-formyl-1-cyclopropanecarboxylate (0.51 mL, 3.86 mmol). The mixture was stirred for 16 hrs at 50° C. The reaction was quenched by the addition of water (100 mL) followed by extraction with diethyl ether (3×100 mL). The combined organic phases were washed with water (3×100 mL), brine (100 mL), dried (MgSO4), filtered, and evaporated in vacuo. The resulting oil was purified by preparative HPLC, dried in vacuo at 50° C. affording 60 mg (8%) of the title compound as a solid. MS-ESI m/z 410; 1H NMR (400 MHz, CDCl3) δ 0.88-1.06 (m, 6H), 1.07-1.20 (m, 4H), 1.25 (t, 3H), 1.27-1.34 (m) and 1.49-1.66 (m, 3H), 1.36-1.48 (m, 2H), 1.72-1.84 (m, 2H), 2.36-2.48 (m, 1H), 2.66-2.76 (m, 1H), 3.18-3.27 (m, 1H), 3.30 (d) and 3.65 (d, 1H), 4.00-4.06 (m) and 4.57-4.65 (m, 1H), 4.14 (q, 2H), 7.18-7.30 (m, 2H), 7.57 (d, 1H), 10.37 (br s, 1H).

Workup

  1. customThe reaction was quenched by the addition of water (100 mL)
  2. extractionfollowed by extraction with diethyl ether (3×100 mL)
  3. washThe combined organic phases were washed with water (3×100 mL), brine (100 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe resulting oil was purified by preparative HPLC
  8. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-3a8684624e734afa91e55e88544b4a25
Source dataset
uspto-grants-2011_11
Patent number
US08053431B2

Linked notes

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