Acetic Acid → 2-[2-(3,4-Difluorophenyl)ethylamino]ethyl carbamic acid tert-butyl ester

HRID 609649Notes

Reaction equation

HRID 609649 reaction equation
[C:1]([O:5][C:6](=[O:11])[NH:7][CH2:8][CH2:9][NH2:10])([CH3:4])([CH3:3])[CH3:2].[F:12][C:13]1[CH:14]=[C:15]([CH2:20][CH:21]=O)[CH:16]=[CH:17][C:18]=1[F:19].C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:11])[NH:7][CH2:8][CH2:9][NH:10][CH2:21][CH2:20][C:15]1[CH:16]=[CH:17][C:18]([F:19])=[C:13]([F:12])[CH:14]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 187201N-BOC-ethylenediamineHCID 5003444Sodium cyanoborohydrideHCID 226673252-(3,4-Difluorophenyl)acetaldehyde

Product 1

HCID 675740992-[2-(3,4-Difluorophenyl)ethylamino]ethyl carbamic acid tert-butyl esterYield 35%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl-N-(2-aminoethyl)carbamate (718 mg, 4.5 mmol) in MeOH (40 mL) at 0° C., under nitrogen, was added (3,4-difluorophenyl)acetaldehyde (0.7 g, 4.5 mmol) in MeOH (10 mL), acetic acid (0.78 mL, 13.5 mmol) and sodium cyanoborohydride (564 mg, 9.0 mmol). After stirring at 0° C. for 15 min the cooling bath was removed and the mixture stirred at room temperature for 3 h. Saturated K2CO3 solution (50 mL) was added and the mixture stirred for a further 15 min. The solvents were removed in vacuo and the residue partitioned between water (50 mL) and EtOAc (2×50 mL). The combined organic layers were dried (Na2SO4), and evaporated. The residue was chromatographed on silica gel, eluting with CH2Cl2 :MeOH:NH3 (90:10:1) to give the amine (473 mg, 35%) as a yellow oil. 1H NMR (250 MHz, CDCl3) δ 1.44 (9H, s), 2.72-2.78 (4H, m), 2.83-2.90 (2H, m), 3.18-3.28 (2H, m), 4.87 (1H, br s), 6.87-7.13 (3H, m). MS (ES+) (301, M+1).

Workup

  1. customwas removed
  2. stirringthe mixture stirred at room temperature for 3 h
  3. additionSaturated K2CO3 solution (50 mL) was added
  4. stirringthe mixture stirred for a further 15 min
  5. customThe solvents were removed in vacuo
  6. customthe residue partitioned between water (50 mL) and EtOAc (2×50 mL)
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. customevaporated
  9. customThe residue was chromatographed on silica gel
  10. washeluting with CH2Cl2 :MeOH:NH3 (90:10:1)

Sources & evidence

ORD record
ord-59cad78e00614fa99c1bdc2726d72bf1
Source dataset
uspto-grants-1999_12
Patent number
US05998415

Reaction notes

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