Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 1-((9-hydroxy-9H-fluoren-9-yl)carbonyl)-N-(2-tert-butyloxycarbonylaminomethyl-5-chlorobenzyl)-L-prolinamide

HRID 1058307Notes

Reaction equation

HRID 1058307 reaction equation
[OH:1][C:2]1([C:15]([N:17]2[CH2:24][CH2:23][CH2:22][C@H:18]2[C:19](O)=[O:20])=[O:16])[C:14]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.[C:25]([O:29][C:30]([NH:32][CH2:33][C:34]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:35]=1[CH2:36][NH2:37])=[O:31])([CH3:28])([CH3:27])[CH3:26].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN1CCOCC1.CN(C)C=O>[OH:1][C:2]1([C:15]([N:17]2[CH2:24][CH2:23][CH2:22][C@H:18]2[C:19]([NH:37][CH2:36][C:35]2[CH:38]=[C:39]([Cl:42])[CH:40]=[CH:41][C:34]=2[CH2:33][NH:32][C:30]([O:29][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:31])=[O:20])=[O:16])[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:8]=2[C:9]2[C:14]1=[CH:13][CH:12]=[CH:11][CH:10]=2

Participants

6

Reactant 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11149921Tert-butyl 2-(aminomethyl)-4-chlorobenzylcarbamateHCID 590382169-hydroxy-9-fluorenylcarbonyl-L-proline

Product 1

HCID 112039571-((9-hydroxy-9H-fluoren-9-yl)carbonyl)-N-(2-tert-butyloxycarbonylaminomethyl-5-chlorobenzyl)-L-prolinamide

Reagents, catalysts & solvents 2

HCID 79724-MethylmorpholineCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 9-hydroxy-9-fluorenylcarbonyl-L-proline (1.8 g, 5.6 mmol) from step 2 above, 2-tert-butoxycarbonylaminomethyl-5-chlorobenzylamine (1.8 g, 6.8 mmol), N-methylmorpholine (12 drops), and benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (3.0 g, 6.7 mmol) in N,N-dimethylformamide (25 mL) was stirred at ambient temperature for 24 hours, concentrated in vacuo, and purified on silica gel (ethyl acetate-hexane, 1:2) to give 1-((9-hydroxy-9H-fluoren-9-yl)carbonyl)-N-(2-tert-butyloxycarbonylaminomethyl-5-chlorobenzyl)-L-prolinamide. HPLC=99%, R.T.=3.69 min, method A; M+1=576.2.

Workup

  1. concentrationconcentrated in vacuo
  2. custompurified on silica gel (ethyl acetate-hexane, 1:2)

Sources & evidence

ORD record
ord-b30d3368703b4791b0b1d4c674a41d6b
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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