N-bromobutanimide → Methyl(2S)-2-[(22S)-8-bromo-17-fluoro-4,18,22,28-tetramethyl-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]-2-(tert-butoxy)acetate

HRID 1482052Notes

Reaction equation

HRID 1482052 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][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:46])[O:23][C:24]2[CH:25]=[C:26]([CH3:45])[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].C1C(=O)N([Br:57])C(=O)C1>CC#N>[Br:57][C:36]1[N:37]2[C:12]3[N:13]4[CH2:48][CH2:47][C:16]([CH3:49])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:46])[O:23][C:24]5[CH:25]=[C:26]([CH3:45])[C:27]([F:44])=[CH:28][C:29]=5[C:30]5[CH:43]=[C:34]([C:35]=1[N:42]=[C:38]2[CH:39]=[C:40]([CH3:41])[C:11]=3[C@H:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[C:7]([O:9][CH3:10])=[O:8])[CH:33]=[CH:32][CH:31]=5)[CH2:15][CH2:14]4

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 118316293Methyl(2S)-2-(tert-butoxy)-2-[(22S)-17-fluoro-4,18,22,28-tetramethyl-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

Product 1

HCID 118316304Methyl(2S)-2-[(22S)-8-bromo-17-fluoro-4,18,22,28-tetramethyl-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]-2-(tert-butoxy)acetateYield 72%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of methyl(2S)-2-(tert-butoxy)-2-[(22S)-17-fluoro-4,18,22,28-tetramethyl-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 (50 mg, 0.074 mmol, 1 equiv) in MeCN (1.5 mL) was added NBS (13 mg, 0.074 mmol, 1 equiv). After 1 h, the reaction was concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc [2% TEA]/hexane) to provide the product (40 mg, 72%). 1H NMR (400 MHz, CHLOROFORM-d) δ 8.16 (s, 1H), 7.82 (d, J=7.8 Hz, 1H), 7.54 (t, J=7.7 Hz, 1H), 7.37 (d, J=7.8 Hz, 1H), 7.29 (s, 1H), 6.97 (d, J=10.3 Hz, 1H), 6.85 (d, J=6.5 Hz, 1H), 4.58-4.37 (m, 2H), 3.82-3.66 (m, 4H), 3.64-3.55 (m, 1H), 3.46-3.38 (m, 1H), 2.47 (br. s., 3H), 2.30 (d, J=0.8 Hz, 4H), 1.98-1.69 (m, 8H), 1.66-1.48 (m, 4H), 1.31-1.26 (m, 7H), 1.24 (d, J=5.8 Hz, 8H), 1.15 (d, J=6.0 Hz, 3H).

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. customThe crude product was purified by flash column chromatography (0-100% EtOAc [2% TEA]/hexane)

Sources & evidence

ORD record
ord-d21e03a96ebb46d58120357eeb11ae53
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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