Hydrochloric Acid → (R)-N,N-Diisopropyl-3-[2-benzyloxy 5-(5-carboxypent-1-enyl)phenyl]-3-phenylpropanamine

HRID 428323Notes

Reaction equation

HRID 428323 reaction equation
[Br-].[C:2]([CH2:5][CH2:6][CH2:7][CH2:8][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:4])=[O:3].C[C:29](C)([O-:31])C.[K+].[CH:34]([N:37]([CH:63]([CH3:65])[CH3:64])[CH2:38][CH2:39][C@@H:40]([C:47]1[CH:52]=[C:51](C=O)[CH:50]=[CH:49][C:48]=1OCC1C=CC=CC=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)([CH3:36])[CH3:35].Cl.C1(P([C:80]2[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:86]1COCC1>C(OCC)C>[CH:63]([N:37]([CH:34]([CH3:35])[CH3:36])[CH2:38][CH2:39][C@@H:40]([C:47]1[CH:52]=[C:51]([CH:86]=[CH:8][CH2:7][CH2:6][CH2:5][C:2]([OH:4])=[O:3])[CH:50]=[CH:49][C:48]=1[O:31][CH2:29][C:80]1[CH:81]=[CH:82][CH:83]=[CH:84][CH:85]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)([CH3:64])[CH3:65]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2×HCID 11776TriphenylphosphineHCID 161236(4-Carboxybutyl)triphenylphosphonium bromideHCID 23665647Potassium tert-butoxideHCID 54206055(R)-N,N-Diisopropyl-3-(2-benzyloxy-5-formylphenyl)-3-phenylpropanamine

Product 1

HCID 54444624(R)-N,N-Diisopropyl-3-[2-benzyloxy 5-(5-carboxypent-1-enyl)phenyl]-3-phenylpropanamine

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a slurry of 4-carboxybutyl triphenylphosphonium bromide (4.1 g, 9.31 mmol) in THF (25 mL) at −10° C. under nitrogen atmosphere was added potassium tert-butoxide (2.1 g, 18.62 mmol). The mixture turned orange and after 10 minutes stirring, (R)-N,N-diisopropyl-3-(2-benzyloxy-5-formylphenyl)-3-phenylpropanamine (2 g, 4.65 mmol) in THF (10 mL) was added. After 4 hours of stirring, hydrochloric acid (1M) and diethyl ether were added and the layers were separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried (MgSO4) and the solvent was evaporated. The residue was chromatographed on silica (ethyl acetate-triethylamine 90:10 followed by methanol) to afford 3 g containing traces of triphenylphosphine. The product was used in the next step without further purification.

Workup

  1. stirringAfter 4 hours of stirring
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. customthe solvent was evaporated
  6. customThe residue was chromatographed on silica (ethyl acetate-triethylamine 90:10 followed by methanol)
  7. customto afford 3 g
  8. customThe product was used in the next step without further purification

Sources & evidence

ORD record
ord-20f408bf8119463d8e5a72d1ca7de827
Source dataset
uspto-grants-2001_11
Patent number
US06313132B1

Reaction notes

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