Sodium Hydroxide → (2S)-2-[(2-methylbutan-2-yl)oxy]-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 1400763Notes

Reaction equation

[CH3:1][C:2]([O:6][C@@H:7]([C:12]1[C:41]([CH3:42])=[N:40][C:39]2=[CH:43][C:36]3=[N:37][N:38]2[C:13]=1[N:14]1[CH2:48][CH2:47][C:17]([CH3:49])([O:18][CH2:19][CH2:20][CH2:21][CH2:22][C@H:23]([CH3:46])[O:24][C:25]2[CH:26]=[CH:27][C:28]([CH3:45])=[CH:29][C:30]=2[C:31]2[CH:44]=[C:35]3[CH:34]=[CH:33][CH:32]=2)[CH2:16][CH2:15]1)[C:8]([O:10]C)=[O:9])([CH2:4][CH3:5])[CH3:3].[OH-].[Na+]>CO>[CH3:1][C:2]([O:6][C@@H:7]([C:12]1[C:41]([CH3:42])=[N:40][C:39]2=[CH:43][C:36]3=[N:37][N:38]2[C:13]=1[N:14]1[CH2:15][CH2:16][C:17]([CH3:49])([O:18][CH2:19][CH2:20][CH2:21][CH2:22][C@H:23]([CH3:46])[O:24][C:25]2[CH:26]=[CH:27][C:28]([CH3:45])=[CH:29][C:30]=2[C:31]2[CH:44]=[C:35]3[CH:34]=[CH:33][CH:32]=2)[CH2:47][CH2:48]1)[C:8]([OH:10])=[O:9])([CH2:4][CH3:5])[CH3:3]

Participants

Conditions

Temperature: 75 °C

Procedure

To a solution of methyl (25)-2-[(2-methylbutan-2-yl)oxy]-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 (10 mg, 0.015 mmol) in MeOH (1 mL) was added 1N NaOH (0.150 mL, 0.150 mmol) solution and the resulting mixture was heated at 75° C. for 3 h. Then, the mixture was cooled and purified by prep HPLC to afford (2S)-2-[(2-methylbutan-2-yl)oxy]-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 (6.4 mg, 9.77 μmol, 65.4% yield). 1H NMR (500 MHz, DMSO-d6) δ 8.50 (s, 1H), 7.92 (d, J=8.2 Hz, 1H), 7.51 (t, J=7.6 Hz, 1H), 7.33 (d, J=7.0 Hz, 1H), 7.17-7.08 (m, 3H), 7.05 (d, J=8.5 Hz, 1H), 5.65 (br. s., 1H), 4.62 (d, J=6.1 Hz, 1H), 4.49 (t, J=12.5 Hz, 1H), 3.64-3.54 (m, 1H), 3.48-3.42 (m, 2H), 2.80 (d, J=10.4 Hz, 1H), 2.29 (s, 3H), 2.03-1.86 (m, 3H), 1.72-1.62 (m, 4H), 1.60-1.41 (m, 5H), 1.19 (s, 3H), 1.15 (s, 3H), 1.11-1.03 (m, 6H), 0.72 (t, J=7.3 Hz, 3H). 4 missing piperidine hydrogens. LCMS (M+H)=655.8.

Workup

temperatureThen, the mixture was cooled
custompurified by prep HPLC

Sources & evidence

ORD record: ord-378451ee6fb7495690586153b486857f
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08906929B2

Reaction notes

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