Isobutylamine → Methyl 5-(benzyloxy)-2-isobutyl-1-oxo-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

HRID 1177366Notes

Reaction equation

HRID 1177366 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([CH2:23][CH:24]=O)=[C:11]([C:19](OC)=[O:20])[CH:12]=[C:13]([CH:18]=1)[C:14]([O:16][CH3:17])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:26](N)[CH:27](C)[CH3:28].[BH3-][C:32]#[N:33].[Na+]>CO>[CH2:1]([O:8][C:9]1[CH:18]=[C:13]([C:14]([O:16][CH3:17])=[O:15])[CH:12]=[C:11]2[C:10]=1[CH2:23][CH2:24][N:33]([CH2:32][CH:27]([CH3:28])[CH3:26])[C:19]2=[O:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6558IsobutylamineHCID 5003444Sodium cyanoborohydrideHCID 59560096Dimethyl 5-(benzyloxy)-4-(2-oxoethyl)isophthalate

Product 1

HCID 59559848Methyl 5-(benzyloxy)-2-isobutyl-1-oxo-1,2,3,4-tetrahydroisoquinoline-7-carboxylateYield 223.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of dimethyl 5-(benzyloxy)-4-(2-oxoethyl)isophthalate (1.5 g, 4.38 mmol) in MeOH was added isobutylamine (385 mg, 0.522 mL, 5.26 mmol). The reaction was stirred at room temperature for 2 hrs, then NaCNBH3 (84.1 mg, 1.34 mmol) was added. The mixture was stirred at 75° C. overnight. The solvents were removed under reduced pressure, diluted with ethyl acetate and washed with brine (3×). The product was purified via gradient silica gel chromatography using MeOH/CHCl3 (5/95 to 10/90) to provide the product (1.1 g, 50% yield) as a film 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.96 (dd, 6H) 1.96-2.16 (m, 1 H) 3.05 (t, J=6.69 Hz, 2 H) 3.36-3.46 (m, J=7.63, 7.63 Hz, 2 H) 3.49-3.62 (m, 2 H) 3.88-4.02 (m, 3 H) 5.16 (s, 2 H) 7.32-7.56 (m, 5 H) 7.74 (d, J=1.32 Hz, 1 H) 8.42 (d, J=1.32 Hz, 1 H); MS (ESI, pos): 368.

Workup

  1. stirringThe mixture was stirred at 75° C. overnight
  2. customThe solvents were removed under reduced pressure
  3. additiondiluted with ethyl acetate
  4. washwashed with brine (3×)
  5. customThe product was purified via gradient silica gel chromatography

Sources & evidence

ORD record
ord-fa66b75cda7447b4a68cdfbfec969915
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

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