Acetic Acid → 2-(N-benzyloxycarbonylpiperidin-4-yl-methyl)amino-5-chloro-alpha-(3-tert-butoxycarbonylaminomethylphenyl)benzyl alcohol

HRID 275864Notes

Reaction equation

HRID 275864 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([CH:17]=O)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)C.[BH4-].C([Na])#N.[NH2:27][C:28]1[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][C:29]=1[CH:30]([OH:46])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH:32]=1>CO>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([CH2:17][NH:27][C:28]2[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][C:29]=2[CH:30]([OH:46])[C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][NH:38][C:39]([O:41][C:42]([CH3:44])([CH3:45])[CH3:43])=[O:40])[CH:32]=2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2776272Benzyl 4-formylpiperidine-1-carboxylateHCID 543588652-Amino-5-chloro-alpha-(3-tert-butoxycarbonylaminomethylphenyl)benzyl alcoholHCID 178511851HCID 178511851, compound

Product 1

HCID 701566552-(N-benzyloxycarbonylpiperidin-4-yl-methyl)amino-5-chloro-alpha-(3-tert-butoxycarbonylaminomethylphenyl)benzyl alcohol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3,5-Trans-N-(2-fluorobenzyl)-1-(N-benzyloxycarbonylpiperidin-4-yl-methyl)-5-(3-tert-butoxycarbonylaminomethylphenyl)-7-chloro-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetamide (1) In methanol (20 ml) were dissolved 2-amino-5-chloro-α-(3-tert-butoxycarbonylaminomethylphenyl)benzyl alcohol produced in Example 1-(2) (1.0 g) and N-benzyloxycarbonyl piperidine-4-carbaldehyde (0.82 g), followed by addition of acetic acid (0.2 g). To the mixture was added, while stirring at room temperature, cyano sodium borohydride (0.2 g). The reaction mixture was stirred for 30 minutes at 60° C., which was then concentrated. To the concentrate was added water (40 ml), followed by extraction with ethyl acetate (60 ml). The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by means of a silica gel column chromatography to give 2-(N-benzyloxycarbonylpiperidin-4-yl-methyl)amino-5-chloro-α-(3-tert-butoxycarbonylaminomethylphenyl)benzyl alcohol (1.5 g) as a colorless oily product.

Workup

  1. additionTo the mixture was added
  2. stirringThe reaction mixture was stirred for 30 minutes at 60° C.
  3. concentrationwhich was then concentrated
  4. additionTo the concentrate was added water (40 ml)
  5. extractionfollowed by extraction with ethyl acetate (60 ml)
  6. washThe organic layer was washed with water
  7. dry with materialdried over anhydrous sodium sulfate
  8. distillationThe solvent was distilled off
  9. customthe residue was purified by means of a silica gel column chromatography

Sources & evidence

ORD record
ord-34e348ffe6ee46dbb28ef15f409f040d
Source dataset
uspto-grants-2002_03
Patent number
US06352982B1

Reaction notes

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