Piperidine → 3-({4-[({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)methyl]phenyl}formamido)propanoic acid

HRID 1633963Notes

Reaction equation

HRID 1633963 reaction equation
[C:1]([NH:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=[O:2].N1CCCCC1.[CH:30]1[C:42]2[CH:41]([CH2:43][O:44][C:45]([NH:47][CH2:48][C:49]3[CH:57]=[CH:56][C:52](C(O)=O)=[CH:51][CH:50]=3)=[O:46])[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[C:34]=2[CH:33]=[CH:32][CH:31]=1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>CN(C=O)C.C(N(CC)C(C)C)C>[CH:30]1[C:42]2[CH:41]([CH2:43][O:44][C:45]([NH:47][CH2:48][C:49]3[CH:50]=[CH:51][C:52]([C:1]([NH:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])=[O:2])=[CH:56][CH:57]=3)=[O:46])[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[C:34]=2[CH:33]=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 8082PiperidineHCID 2724630N-Fluorenylmethoxycarbonyl-I2-alanineHCID 2733179PyBroPHCID 27560834-(((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)methyl)benzoic acid

Product 1

HCID 225021983-({4-[({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)methyl]phenyl}formamido)propanoic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 521913N,N-Diethyl-2-propanamineSolvent

Procedure

To the above resin bound Fmoc β-alanine was added 500 μL of a 20% solution of piperidine in DMF. Upon shaking for 30 min, the resin was drained and washed with 1 mL DMF containing 1-hydroxybenzotriazole (50 mg/mL) and DMF (2×1 mL). Then 200 μmol 4-[(9H-fluoren-9-ylmethoxycarbonylamino)methyl]benzoic acid (74.2 mg) dissolved in a mixture of 430 μL DMF and 70 μL diethylisopropylamine was added followed by 200 μmol bromo-tris-pyrrolidinophosphonium hexafluorophosphate (PyBrOP, 93 mg) dissolved in 500 μL DMF. The mixture was shaken for 4 hours at 25° C. followed by filtration and washing of the resin with 3×1 mL DMF.

Workup

  1. washwashed with 1 mL DMF
  2. additioncontaining 1-hydroxybenzotriazole (50 mg/mL) and DMF (2×1 mL)
  3. additionwas added
  4. stirringThe mixture was shaken for 4 hours at 25° C.
  5. filtrationfollowed by filtration
  6. washwashing of the resin with 3×1 mL DMF

Sources & evidence

ORD record
ord-1298ed63956c4567b4b49f9e236a7d7b
Source dataset
uspto-grants-2003_01
Patent number
US06503949B1

Reaction notes

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