Sodium Hydroxide → (2S)-2-(1-methylcyclobutoxy)-2-[(22S)-4,17,22,28-tetramethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetic acid

HRID 1400765Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1400765
[OH:1][C@@H:2]([C:7]1[C:36]([CH3:37])=[N:35][C:34]2=[CH:38][C:31]3=[N:32][N:33]2[C:8]=1[N:9]1[CH2:43][CH2:42][C:12]([CH3:44])([O:13][CH2:14][CH2:15][CH2:16][CH2:17][C@H:18]([CH3:41])[O:19][C:20]2[CH:21]=[CH:22][C:23]([CH3:40])=[CH:24][C:25]=2[C:26]2[CH:39]=[C:30]3[CH:29]=[CH:28][CH:27]=2)[CH2:11][CH2:10]1)[C:3]([O:5]C)=[O:4].C(O[C:49]1([CH3:53])[CH2:52][CH2:51][CH2:50]1)(=O)C.Cl(O)(=O)(=O)=O.[OH-].[Na+]>C(Cl)Cl.CO>[CH3:53][C:49]1([O:1][C@@H:2]([C:7]2[C:36]([CH3:37])=[N:35][C:34]3=[CH:38][C:31]4=[N:32][N:33]3[C:8]=2[N:9]2[CH2:43][CH2:42][C:12]([CH3:44])([O:13][CH2:14][CH2:15][CH2:16][CH2:17][C@H:18]([CH3:41])[O:19][C:20]3[CH:21]=[CH:22][C:23]([CH3:40])=[CH:24][C:25]=3[C:26]3[CH:39]=[C:30]4[CH:29]=[CH:28][CH:27]=3)[CH2:11][CH2:10]2)[C:3]([OH:5])=[O:4])[CH2:52][CH2:51][CH2:50]1

Komponenten

7

Edukt 4

HCID 14798Sodium HydroxideHCID 24247Perchloric AcidHCID 133961301-Methylcyclobutyl acetateHCID 86710817methyl (2S)-2-hydroxy-2-[(22S)-4,17,22,28-tetramethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15 (20),16,18-decaen-3-yl]acetate

Produkt 1

HCID 73386953(2S)-2-(1-methylcyclobutoxy)-2-[(22S)-4,17,22,28-tetramethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetic acidAusbeute 36,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a stirred solution of methyl (2S)-2-hydroxy-2-[(22S)-4,17,22,28-tetramethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate (40 mg, 0.067 mmol) in DCM (2 mL) and 1-methylcyclobutyl acetate (599 mg, 4.68 mmol) at rt was added 70 wt % perchloric acid (0.017 mL, 0.200 mmol). After 3 h, the reaction mixture was diluted with DCM (25 mL), carefully quenched with sat. NaHCO3 (5 mL), organic layer separated and washed with brine (10 mL), dried (Na2SO4), filtered and concentrated to give yellow paste. The crude was then tretated with 1N NaOH (0.334 mL, 0.334 mmol) in MeOH (1 mL) at 75° C. for 3 h. Mixture was then cooled and purified by prep HPLC to afford (2S)-2-(1-methylcyclobutoxy)-2-[(22S)-4,17,22,28-tetramethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetic acid (15.8 mg, 0.024 mmol, 36.2% yield). 1H NMR (500 MHz, DMSO-d6) δ 8.52 (s, 1H), 7.91 (d, J=7.9 Hz, 1H), 7.51 (t, J=7.6 Hz, 1H), 7.33 (d, J=7.6 Hz, 1H), 7.17-7.11 (m, 2H), 7.08 (s, 1H), 7.05 (d, J=8.2 Hz, 1H), 5.49 (s, 1H), 4.62 (d, J=5.5 Hz, 1H), 4.45 (t, J=12.2 Hz, 1H), 3.61-3.53 (m, 1H), 3.40-3.20 (m, 7H), 2.83 (d, J=10.4 Hz, 1H), 2.29 (s, 3H), 2.22 (q, J=10.0 Hz, 1H), 2.01-1.86 (m, 4H), 1.82 (br. s., 1H), 1.70-1.62 (m, 5H), 1.58-1.41 (m, 4H), 1.28 (s, 3H), 1.17 (s, 3H), 1.07 (d, J=5.8 Hz, 3H). LCMS (M+H)=653.6.

Aufarbeitung

  1. customcarefully quenched with sat. NaHCO3 (5 mL), organic layer
  2. customseparated
  3. washwashed with brine (10 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give yellow paste
  8. temperatureMixture was then cooled
  9. custompurified by prep HPLC

Quellen und Nachweise

ORD-Eintrag
ord-721b30c6d237473bbb5b039759411668
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08906929B2

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