Formaldehyde → benzyl((1R,2S)-2-{[((2RS)-6-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl)(methyl)amino]methyl}cyclohexyl)carbamate

HRID 1592340Notes

Reaction equation

HRID 1592340 reaction equation
[CH2:1]([O:8][C:9](=[O:30])[NH:10][C@@H:11]1[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]1[CH2:17][NH:18][CH:19]1[CH2:28][CH2:27][C:26]2[C:21](=[CH:22][CH:23]=[C:24]([F:29])[CH:25]=2)[CH2:20]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[C:33]([BH3-])#N.[Na+].[OH-].[Na+]>C(#N)C.C(O)(=O)C>[CH2:1]([O:8][C:9](=[O:30])[NH:10][C@@H:11]1[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]1[CH2:17][N:18]([CH:19]1[CH2:28][CH2:27][C:26]2[C:21](=[CH:22][CH:23]=[C:24]([F:29])[CH:25]=2)[CH2:20]1)[CH3:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 131726668benzyl((1R,2S)-2-{[((2RS)-6-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino]methyl}cyclohexyl)carbamate

Product 1

HCID 131726669benzyl((1R,2S)-2-{[((2RS)-6-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl)(methyl)amino]methyl}cyclohexyl)carbamateYield 90.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of benzyl((1R,2S)-2-{[((2RS)-6-fluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino]methyl}cyclohexyl)carbamate (300 mg, 0.73 mmol) in acetonitrile (4 mL) was treated with formaldehyde (37% aqueous, 300 μL), sodium cyanoborohydride (138 mg, 2.19 mmol) and a few drops of acetic acid. After stirring at room temperature, the mixture was treated with aqueous sodium hydroxide (1.0 N) and extracted with dichloromethane. The organic phase was dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography, eluting with 5% methanol in dichloromethane containing 0.5% aqueous ammonia, to provide a gum (280 mg, 90%).

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography
  5. washeluting with 5% methanol in dichloromethane containing 0.5% aqueous ammonia

Sources & evidence

ORD record
ord-1b956bfb41ed4bd8b5c357be005ebcc4
Source dataset
uspto-grants-2007_11
Patent number
US07291744B2

Reaction notes

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