Methyl(2S)-2-(tert-butoxy)-2-[(22S)-18-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[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 → Methyl(2S)-2-(tert-butoxy)-2-[(22S)-17,18-difluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[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 1482018Notes

Reaction equation

[C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[CH:39][C:38]2=[N:42][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:48][CH2:47][C:16]([CH3:49])([O:17][CH2:18][CH:19]=[CH:20][CH2:21][C@H:22]([CH3:46])[O:23][C:24]2[CH:25]=[C:26]([F:45])[C:27]([F: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])([CH3:4])([CH3:3])[CH3:2].C(O[C@@H](C1C(C)=CC2=NC3=CN2C=1N1CCC(C)(OCCCC[C@H](C)OC2C=C(F)C=CC=2C2C=C3C=CC=2)CC1)C(OC)=O)(C)(C)C>>[C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[CH:39][C:38]2=[N:42][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:14][CH2:15][C:16]([CH3:49])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:46])[O:23][C:24]2[CH:25]=[C:26]([F:45])[C:27]([F:44])=[CH:28][C:29]=2[C:30]2[CH:43]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:47][CH2:48]1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

Reactant 2

HCID 118316270Methyl(2S)-2-(tert-butoxy)-2-[(22S)-18-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[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

HCID 123534084Methyl(2S)-2-(tert-butoxy)-2-[(22S)-17,18-difluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18,24-undecaen-3-yl]acetate

Product 1

HCID 118316281Methyl(2S)-2-(tert-butoxy)-2-[(22S)-17,18-difluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[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 75%

Procedure

Prepared in 75% yield from methyl(2S)-2-(tert-butoxy)-2-[(22S)-17,18-difluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18,24-undecaen-3-yl]acetate following the same procedure as methyl(2S)-2-(tert-butoxy)-2-[(22S)-18-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[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. 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J=8.0 Hz, 1H), 8.08 (s, 1H), 8.02 (s, 1H), 7.53 (t, J=7.7 Hz, 1H), 7.32 (s, 1H), 7.27-7.16 (m, 2H), 6.82 (dd, J=12.7, 6.9 Hz, 1H), 6.04 (br. s., 1H), 4.44 (d, J=5.0 Hz, 1H), 3.96 (t, J=11.0 Hz, 1H), 3.81-3.72 (m, 1H), 3.70 (s, 3H), 3.57-3.42 (m, 2H), 3.10 (d, J=10.5 Hz, 1H), 2.70 (d, J=10.8 Hz, 1H), 2.46 (s, 3H), 2.00-1.70 (m, 10H), 1.29 (s, 3H), 1.25 (s, 9H), 1.16 (d, J=6.0 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −137.12-−137.51 (m, 1F), −148.56-−149.02 (m, 1F); LCMS (ESI, M+1): 676.25.

Sources & evidence

ORD record: ord-67c133456b4a4b9a81bedeca45f47389
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409922B2

Reaction notes

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