Ethyl oxoacetate → Ethyl 2-(1-(1-(4-chlorophenyl)cyclobutyl)-3-methylbutylamino]acetate

HRID 623367Notes

Reaction equation

HRID 623367 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH:12]([NH2:17])[CH2:13][CH:14]([CH3:16])[CH3:15])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:18]([O:22][CH2:23][CH3:24])(=[O:21])[CH:19]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(O)(=O)C.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH:12]([NH:17][CH2:19][C:18]([O:22][CH2:23][CH3:24])=[O:21])[CH2:13][CH:14]([CH3:15])[CH3:16])[CH2:11][CH2:10][CH2:9]2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 70211Ethyl oxoacetateHCID 134772DidesmethylsibutramineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 25050583Ethyl 2-(1-(1-(4-chlorophenyl)cyclobutyl)-3-methylbutylamino]acetate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of cyclobutane amine 52a (0.68 g, 0.0027 mole) and ethyl glyoxylate (50% solution in toluene) (1.02 g, 0.01 mole) in 20 mL of a mixture of solvents DMF and acetic acid (ratio, 99:1) was added sodium triacetoxyborohydride (2.11 g, 0.01 mole) portion-wise over a period of 15 minutes at room temperature. The resulting mixture was stirred for 8 hours at room temperature and the progress of the reaction was monitored by TLC. The reaction mixture was poured in to saturated sodium bicarbonate solution (50 mL) and extracted with ethyl acetate (50 mL×3). The combined extract was washed with water (50 mL), dried over sodium sulfate (Na2SO4) and evaporated. The residue was purified by silica gel column chromatography using 0-50% gradient of ethyl acetate and hexane as eluents to give pure 54a as colorless liquid in 45% (0.41 g) yield. The 1H NMR and mass spectral data are identical to the compound synthesized using the protocol described for the synthesis of 54a-e (Example 3, Scheme 7).

Workup

  1. extractionextracted with ethyl acetate (50 mL×3)
  2. extractionThe combined extract
  3. washwas washed with water (50 mL)
  4. dry with materialdried over sodium sulfate (Na2SO4)
  5. customevaporated
  6. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a812c5ac6e23473ca30dbbb0cd49383e
Source dataset
uspto-grants-2016_04
Patent number
US09302981B2

Reaction notes

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