Sodium Bicarbonate → methyl 2-acetylamino-4-[2-(N-tert-butoxycarbonyl-N-methylamino)ethylamino]benzoate

HRID 354513Notes

Reaction equation

HRID 354513 reaction equation
[C:1]([NH:4][C:5]1[CH:14]=[C:13]([NH2:15])[CH:12]=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8])(=[O:3])[CH3:2].[C:16]([O:20][C:21]([N:23]([CH3:27])[CH2:24][CH:25]=O)=[O:22])([CH3:19])([CH3:18])[CH3:17].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[C:1]([NH:4][C:5]1[CH:14]=[C:13]([NH:15][CH2:25][CH2:24][N:23]([C:21]([O:20][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:22])[CH3:27])[CH:12]=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 10725881tert-butyl N-methyl-N-(2-oxoethyl)carbamateHCID 12399498Methyl 2-acetylamino-4-aminobenzoate

Product 1

HCID 23512140methyl 2-acetylamino-4-[2-(N-tert-butoxycarbonyl-N-methylamino)ethylamino]benzoateYield 86%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a cooled solution of methyl 2-acetylamino-4-aminobenzoate (300 mg, 1.44 mmol) and N-tert-butoxycarbonyl-N-methylglycinal (499 mg, 2.88 mmol) in 1,2dichloroethane (30 ml), was added NaBH(OAc)3 (964 mg, 4.32 mmol) and the stirring was continued for 64 h at 0° C. The mixture was poured into sat. NaHCO3 and was extracted with CHCl3 (50 ml×3), washed with brine, and dried over MgSO4. After removal of the solvent in vacuo, the residue was chromatographed on silica gel (middle pressure chromatography system: YAMAZEN YFLC-5404-FC, linear gradient of hexane-EtOAc from 9:1 to 2:1) to give methyl 2-acetylamino-4-[2-(N-tert-butoxycarbonyl-N-methylamino)ethylamino]benzoate (451 mg, 86%) as a colorless oil. 1H-NMR (CDCl3, 400 MHz) δ1.48 (s, 9 H), 2.22 (s, 3 H), 2.90 (s, 3 H), 3.32 (m, 2 H), 3.50 (m, 2 H), 3.80 (s, 3 H), 6.20 (dd, J=2.2 Hz, 8.8 Hz, 1H), 7.80 (m, 1H, 7.95 (m, 1H), 11.30 (brs, 1 H); MS (FAB) m/z 366 (M++1).

Workup

  1. extractionwas extracted with CHCl3 (50 ml×3)
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. customAfter removal of the solvent in vacuo
  5. customthe residue was chromatographed on silica gel (middle pressure chromatography system: YAMAZEN YFLC-5404-FC, linear gradient of hexane-EtOAc from 9:1 to 2:1)

Sources & evidence

ORD record
ord-1f1206f3aac24d04a35dd77a09de8d95
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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