Methanamine, N-methoxy-, hydrochloride (1:1) → HCID 86585078, Verbindung

HRID 1264428Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1264428
[SH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][CH2:10][C:11]2[C:23]3[CH2:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[C:15]=3[CH:14]=[CH:13][CH:12]=2)=[O:8])[C@H:4]([C:24](O)=[O:25])[CH2:3]1.[B-](F)(F)(F)F.CN(C(ON1C(=O)C=CC=C1)=[N+](C)C)C.CCN(C(C)C)C(C)C.Cl.CNOC.[F:61][C:62]1[CH:67]=[CH:66][C:65]([Mg]Br)=[CH:64][CH:63]=1>CN(C=O)C.C1COCC1>[CH:13]1[C:12]2[CH:11]([CH2:10][O:9][C:7]([N:5]3[CH2:6][C@H:2]([SH:1])[CH2:3][C@H:4]3[C:24](=[O:25])[C:65]3[CH:66]=[CH:67][C:62]([F:61])=[CH:63][CH:64]=3)=[O:8])[C:20]3[C:21](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:22]=2[CH:23]=[CH:15][CH:14]=1

Komponenten

8

Edukt 5

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 2733204O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 86585079HCID 86585079, VerbindungHCID 178418676HCID 178418676, Verbindung

Produkt 1

HCID 86585078HCID 86585078, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

Resin derivatized with (2S,4R)-4-sulfanyl-1-(fluorenylmethoxycarbonyl)-pyrrolidine-2-carboxylic acid (9.71 g, 5.73 mmol) above, was treated with DMF (abs. 80 ml), TPTU (3.4 g, 11.46 mmol), DIEA (2.94 ml, 17.2 mmol) for 15 min. The DMF solution was removed under vacuum and the reaction flask was charged with N,O-dimethylhydroxylamine.hydrochloride (1.68 g, 17.2 mmol) in DMF (abs. 80 ml). The reaction mixture was shaken for 2 h and the resin was collected at the filter, washed (3× alternating DMF/isopropanol), DMF. The resin (1.0 g, 0.6 mmol) was washed with THF(abs.2×) under an argon overpressure resuspended in THF (abs. 8 ml) and treated with 4-fluorophenyl magnesiumbromide (1M in THF, 5.9 ml). After 4 h the resin was filtered off and washed with THF. 0.5 N KHSO4 was added and the reaction flask was shaken for 15 min. The resin was further washed DMF, 0.5 N KHSO4, (alternating DMF, MeOH, H2O ), DMF, CH2Cl2, diethyl ether and dried. The resin (0.38 mg) was treated with 40% TFA/CH2Cl2 (10 ml), triisopropylsilane (0.5 ml) for 1 h and the filtrate was collected and concentrated under reduced pressure and the residue was purified by prep.RP-HPLC and the desired fractions were pooled and freeze-dried from acetic acid (10 ml) yielding (2S,4R)-2-(4-fluoro-benzoyl)-4-mercapto-pyrrolidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester MS: 448.3 (MH+).

Aufarbeitung

  1. customThe DMF solution was removed under vacuum
  2. customthe resin was collected at the filter
  3. washwashed (3× alternating DMF/isopropanol), DMF
  4. filtrationAfter 4 h the resin was filtered off
  5. washwashed with THF
  6. addition0.5 N KHSO4 was added
  7. stirringthe reaction flask was shaken for 15 min
  8. customdried
  9. additionThe resin (0.38 mg) was treated with 40% TFA/CH2Cl2 (10 ml), triisopropylsilane (0.5 ml) for 1 h
  10. customthe filtrate was collected
  11. concentrationconcentrated under reduced pressure
  12. customthe residue was purified by prep.RP-HPLC and the desired fractions
  13. dry with materialfreeze-dried from acetic acid (10 ml)

Quellen und Nachweise

ORD-Eintrag
ord-519f6ff8c821459999c9837ef9581a1d
Quelldatensatz
uspto-grants-2003_04
Patentnummer
US06541638B2

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