Trifluoroacetic acid → 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

HRID 1400761Notes

Reaction equation

HRID 1400761 reaction equation
C([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[N:39][C:38]2=[CH:42][C:35]3=[N:36][N:37]2[C:12]=1[N:13]1[CH2:47][CH2:46][C:16]([CH3:48])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:45])[O:23][C:24]2[CH:25]=[CH:26][C:27]([CH3:44])=[CH:28][C:29]=2[C:30]2[CH:43]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:15][CH2:14]1)[C:7]([O:9][CH3:10])=[O:8])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[N:39][C:38]2=[CH:42][C:35]3=[N:36][N:37]2[C:12]=1[N:13]1[CH2:47][CH2:46][C:16]([CH3:48])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:45])[O:23][C:24]2[CH:25]=[CH:26][C:27]([CH3:44])=[CH:28][C:29]=2[C:30]2[CH:43]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:15][CH2:14]1)[C:7]([O:9][CH3:10])=[O:8]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86710818methyl (2S)-2-(tert-butoxy)-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

Product 1

HCID 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]acetateYield 74.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl (2S)-2-(tert-butoxy)-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 (88 mg, 0.134 mmol) in DCM (3 mL) at room temp was added TFA (0.311 mL, 4.03 mmol) and the mixture was stirred at room temp for 16 h. Then, mixture was concentrated and purified by biotage (0-40% EtOAc/hexane) to afford 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 (60 mg, 0.100 mmol, 74.6% yield) as viscous oil. 1H NMR (500 MHz, CDCl3) δ 8.53-8.42 (m, 1H), 7.79 (d, J=7.7 Hz, 1H), 7.50 (t, J=7.6 Hz, 1H), 7.36 (d, J=7.6 Hz, 1H), 7.16-7.11 (m, 2H), 6.96-6.85 (m, 2H), 5.56 (s, 1H), 4.62-4.38 (m, 2H), 4.15 (q, J=7.1 Hz, 1H), 3.89-3.83 (m, 1H), 3.81 (s, 3H), 3.47 (br. s., 1H), 3.41-3.29 (m, 1H), 3.18 (d, J=10.9 Hz, 1H), 2.76 (d, J=11.8 Hz, 1H), 2.66 (s, 2H), 2.36 (s, 3H), 2.05-1.96 (m, 1H), 1.90 (t, J=12.5 Hz, 2H), 1.82-1.72 (m, 2H), 1.68-1.56 (m, 2H), 1.50 (br. s., 2H), 1.29 (t, J=7.1 Hz, 2H), 1.24 (s, 3H), 1.15 (d, J=6.0 Hz, 3H). LCMS (M+H)=599.4.

Workup

  1. concentrationThen, mixture was concentrated
  2. custompurified by biotage (0-40% EtOAc/hexane)

Sources & evidence

ORD record
ord-162f1105f78146a9b5117b322143d9e0
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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