Acetic Acid → {4-[(4-Bromo-phenylamino)-methyl]-tetrahydro-pyran-4-yl}-carbamic acid tert-butyl ester

HRID 1968876Notes

Reaction equation

HRID 1968876 reaction equation
[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1([CH:14]=O)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[Br:17][C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][CH:19]=1.C(O)(=O)C.C([BH3-])#N.[Na+]>C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1([CH2:14][NH:22][C:21]2[CH:23]=[CH:24][C:18]([Br:17])=[CH:19][CH:20]=2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 78074-BromoanilineHCID 5003444Sodium cyanoborohydrideHCID 59718793(4-Formyltetrahydropyran-4-yl)carbamic acid tert-butyl ester

Product 1

HCID 67114132{4-[(4-Bromo-phenylamino)-methyl]-tetrahydro-pyran-4-yl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of (4-formyl-tetrahydro-pyran-4-yl)-carbamic acid tert-butyl ester (4.48 g, 19.5 mmol), 4-bromoaniline (3.38 g, 19.7 mmol), and acetic acid (1.2 mL, 21.2 mmol) in ethyl acetate (50 mL) contained in a 250 mL round bottom flask fitted with a reflux condenser and a Dean and Stark trap was heated at reflux under N2 blanket for 2 h then cooled to ambient temperature. Sodium cyanoborohydride (1.29 g, 19.5 mmol) was added and the mixture stirred over night. The reaction mixture was then washed with water (50 mL), saturated aqueous sodium chloride (50 mL), dried (MgSO4), preabsorbed on silica gel and flash chromatographed (elution solvent: 10% (v/v) ethyl acetate/hexane) to isolate the desired product as 3.1 g of white solid foam. LRMS (ESI) m/z 385.0, 387.0 [(M+H)+, calcd for C17H26N2O3Br 386.3].

Workup

  1. customfitted with a reflux condenser
  2. temperaturea Dean and Stark trap was heated
  3. temperatureat reflux under N2 blanket for 2 h
  4. washThe reaction mixture was then washed with water (50 mL), saturated aqueous sodium chloride (50 mL)
  5. dry with materialdried (MgSO4)
  6. custompreabsorbed on silica gel and flash
  7. customchromatographed
  8. wash(elution solvent: 10% (v/v) ethyl acetate/hexane)

Sources & evidence

ORD record
ord-ffb804d4a8cd4e9297b336b0739fa134
Source dataset
uspto-grants-2013_04
Patent number
US08426414B2

Reaction notes

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