Formaldehyde → 1,1-Dimethylethyl [5-(methylamino)-2-(methyloxy)phenyl]carbamate

HRID 1014389Notes

Reaction equation

HRID 1014389 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:16][CH3:17])=[C:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:7]=1.[CH2:18]=O.C[O-].[Na+].[BH4-].[Na+]>CO.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>[CH3:18][NH:1][C:2]1[CH:3]=[CH:4][C:5]([O:16][CH3:17])=[C:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:13])[CH3:14])[CH:7]=1

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 4311764Sodium borohydrideHCID 10942334Sodium MethoxideHCID 22344747tert-butyl N-(5-amino-2-methoxyphenyl)carbamate

Product 1

HCID 594418351,1-Dimethylethyl [5-(methylamino)-2-(methyloxy)phenyl]carbamateYield 104.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
50 °C

Procedure

A suspension of 1,1-dimethylethyl [5-amino-2-(methyloxy)phenyl]carbamate (1.94 g, 8.14 mmol), paraformaldehyde (1.222 g, 40.7 mmol), and sodium methoxide (2.199 g, 40.7 mmol) in methanol (50 ml) was maintained at 50° C. for 16 hours, cooled, sodium borohydride (0.924 g, 24.42 mmol) was added portionwise, and the solution was re-heated to 50° C. and maintained for an additional 24 hours. The solution was cooled, diluted with ethyl acetate, saturated sodium bicarbonate, and the organic layer was dried over sodium sulfated, filtered, taken to a residue under reduced pressure, and purified by column chromatography to afford 1,1-dimethylethyl [5-(methylamino)-2-(methyloxy)phenyl]carbamate (2.15 g, 8.52 mmol, quant. Yield) as a pale yellow oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.58 (s, 1 H), 7.10 (d, J=1.6 Hz, 1 H), 6.76 (d, J=8.8 Hz, 1 H), 6.14 (dd, J=8.7, 2.7 Hz, 1H), 5.07-5.31 (m, 1 H), 3.61-3.74 (m, 3 H), 2.60 (d, J=4.4 Hz, 3 H), 1.44 (s, 9 H).

Workup

  1. temperaturecooled
  2. temperaturethe solution was re-heated to 50° C.
  3. temperaturemaintained for an additional 24 hours
  4. temperatureThe solution was cooled
  5. dry with materialthe organic layer was dried over sodium
  6. filtrationfiltered
  7. custompurified by column chromatography

Sources & evidence

ORD record
ord-86ff43889252450e9139978a77ad0a01
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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