Trifluoroacetic acid → HCID 69588123, compound

HRID 1797124Notes

Reaction equation

HRID 1797124 reaction equation
C(OC([NH:8][C@@H:9]([C:17]([OH:19])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=O)(C)(C)C.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[C:42]1([CH:48]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[CH2:49][NH2:50])[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.FC(F)(F)C(O)=O>C(Cl)(Cl)Cl.C(Cl)Cl.CCOCC>[NH2:8][C@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:17]([NH:50][CH2:49][CH:48]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)=[O:19]

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 775752,2-DiphenylethylamineHCID 637610Boc-D-phenylalanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 69588123HCID 69588123, compoundYield 111%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6212ChloroformSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-(tert-butoxycarbonyl)-D-phenylalanine (11.0 g, 41.5 mmol) in chloroform (125 mL) was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (7.95 g, 41.5 mmol) and 1-hydroxybenzotriazole (5.60 g, 41.4 mmol). After 5 minutes, 2,2-diphenylethylamine (7.44 g, 37.7 mmol) was added. The reaction was stirred for 2 hours, diluted with chloroform (100 mL) and washed with aqueous sodium bicarbonate solution. The organic layer was dried (sodium sulfate) and concentrated to afford an off-white solid. Trituration with ether afforded the crude amide. This material was taken up in methylene chloride (100 mL) and treated with trifluoroacetic acid (45 mL, 580 mmol). After stirring for 15 minutes, the reaction was concentrated and the residue was partitioned between ethyl acetate and aqueous sodium bicarbonate. The organic layer was dried (sodium sulfate) and concentrated to afford 12.4 g (111% yield inflated by entrained residual solvent) of product as a colorless gum: 1H NMR (CDCl3) δ 7.34–6.95 (m, 15H), 4.10 (t, J=8.2, 1H), 3.88–3.79 (m, 2H), 3.68–3.61 (m, 1H), 3.49 (br s, 2H), 3.13–3.03 (m, 1H), 2.70–2.59 (m, 1H) ppm.

Workup

  1. washwashed with aqueous sodium bicarbonate solution
  2. dry with materialThe organic layer was dried (sodium sulfate)
  3. concentrationconcentrated
  4. customto afford an off-white solid
  5. stirringAfter stirring for 15 minutes
  6. concentrationthe reaction was concentrated
  7. customthe residue was partitioned between ethyl acetate and aqueous sodium bicarbonate
  8. dry with materialThe organic layer was dried (sodium sulfate)
  9. concentrationconcentrated
  10. customto afford 12.4 g (111% yield inflated by entrained residual solvent) of product as a colorless gum

Sources & evidence

ORD record
ord-3b9b4dd5815c48a6854f5c39fb39d9e7
Source dataset
uspto-grants-2006_04
Patent number
US07034031B2

Reaction notes

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