Acetic Anhydride → 4-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine

HRID 1281028Notes

Reaction equation

HRID 1281028 reaction equation
NC1C=C(C=CC=1O)C[N:6]1[CH2:11][CH2:10][CH:9]([CH2:12][NH:13][C:14](=[O:35])[CH2:15][NH:16][C:17](=[O:34])[C:18]2[CH:23]=[C:22]([F:24])[C:21]([F:25])=[CH:20][C:19]=2[NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:8][CH2:7]1.C1CCNCC1.C(OC(=O)C)(=O)C>ClCCl>[C:30]([O:29][C:27]([NH:26][C:19]1[CH:20]=[C:21]([F:25])[C:22]([F:24])=[CH:23][C:18]=1[C:17]([NH:16][CH2:15][C:14]([NH:13][CH2:12][CH:9]1[CH2:10][CH2:11][NH:6][CH2:7][CH2:8]1)=[O:35])=[O:34])=[O:28])([CH3:33])([CH3:31])[CH3:32]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8082PiperidineHCID 184262671-(3-amino-4-hydroxybenzyl)-4-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine

Product 1

HCID 184262024-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidineYield 143.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 1-(3-amino-4-hydroxybenzyl)-4-[{N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl}aminomethyl]piperidine (27 mg, 0.049 mmol), (piperidinomethyl)polystyrene (2.7 mmol/g, 60 mg, 0.15 mmol) and dichloromethane (2 mL) was added acetic anhydride (0.12 mmol) in dichloromethane (0.12 mL). The reaction mixture was stirred at room temperature for 3 h. The mixture was loaded onto Varian™ SCX column, and washed with CH3OH. Product was eluted off using 2 N NH3 in CH3OH and concentrated to give 1-(3-acetylamino)-4-hydroxybenzyl)-4-[{N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl}aminomethyl]piperidine (30 mg, quant.): ESI/MS m/e 590.4 (M++H, C29H37F2N5O6).

Workup

  1. washwashed with CH3OH
  2. washProduct was eluted off
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-ea0df486b9c649d2a9c1a31661a12af4
Source dataset
uspto-grants-2002_09
Patent number
US06451842B1

Reaction notes

Loading…