HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

4-Methylmorpholine → tert-butyl (5S,8S,11S,12R)-11-((S)-sec-butyl)-1-(9H-fluoren-9-yl)-5,8-diisopropyl-12-methoxy-4,10-dimethyl-3,6,9-trioxo-2-oxa-4,7,10-triazatetradecan-14-oate

HRID 74721
Notes
Print preview

Reaction equation

HRID 74721 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([N:18]([CH3:26])[C@H:19]([C:23](O)=[O:24])[CH:20]([CH3:22])[CH3:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH3:27][O:28][C@@H:29]([C@@H:38]([N:43]([CH3:51])[C:44](=[O:50])[C@H:45]([CH:47]([CH3:49])[CH3:48])[NH2:46])[C@@H:39]([CH3:42])[CH2:40][CH3:41])[CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1>CC1CCCO1>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([N:18]([CH3:26])[C@H:19]([C:23]([NH:46][C@H:45]([C:44]([N:43]([C@@H:38]([C@@H:39]([CH3:42])[CH2:40][CH3:41])[C@H:29]([O:28][CH3:27])[CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:35])[CH3:36])=[O:32])[CH3:51])=[O:50])[CH:47]([CH3:49])[CH3:48])=[O:24])[CH:20]([CH3:21])[CH3:22])=[O:17])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 978328(2S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-methylbutanoic acidHCID 10546343(3R,4S,5S)-tert-butyl 4-((S)-2-amino-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoate

Product 1

HCID 71294595
tert-butyl (5S,8S,11S,12R)-11-((S)-sec-butyl)-1-(9H-fluoren-9-yl)-5,8-diisopropyl-12-methoxy-4,10-dimethyl-3,6,9-trioxo-2-oxa-4,7,10-triazatetradecan-14-oate
Yield 108.4%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Procedure

To a mixture of N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-methyl-L-valine (19.54 g, 55.29 mmol, 1.3 eq.) and #6 (15.25 g, 42.54 mmol, 1 eq.) in 2-methyltetrahydrofuran (152 mL, 0.28 M) was added 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) (9.71 g, 55.3 mmol, 1.3 eq.). After 10 minutes, N-methylmorpholine (6.6 mL, 60 mmol, 1.4 eq.) was slowly added, while keeping the internal temp below 25° C. The reaction was stirred for 4 hours and was then quenched by the addition of water (50 mL). After stirring for 15 minutes, the aqueous layer was separated and back-extracted with 2-methyltetrahydrofuran (50 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution (100 mL), then were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting yellow foam was purified by silica gel chromatography (Gradient: 5% to 35% ethyl acetate in heptane) to give #7 (32 g, 97%). 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ 7.89 (d, J=7.4 Hz, 2H), 7.62 (d, J=7.4 Hz, 2H), 7.41 (br dd, J=7.4, 7.4 Hz, 2H), 7.29-7.34 (m, 2H), 4.52-4.69 (br m, 1H), 3.70-3.82 (br m, 1H), 3.22 and 3.25 (2 br s, total 3H), 2.94 and 2.96 (2 br s, total 3H), 2.78 and 2.81 (2 br s, total 3H), 2.11-2.23 (m, 1H), 1.90-2.10 (m, 2H), 1.68-1.83 (br m, 1H), 1.40 (s, 9H), 1.21-1.33 (br m, 1H).

Workup

  1. customthe internal temp below 25° C
  2. customwas then quenched by the addition of water (50 mL)
  3. stirringAfter stirring for 15 minutes
  4. customthe aqueous layer was separated
  5. extractionback-extracted with 2-methyltetrahydrofuran (50 mL)
  6. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution (100 mL)
  7. dry with materialwere dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting yellow foam was purified by silica gel chromatography (Gradient: 5% to 35% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-b9d0aa9ac2ed498bb7c6ce44bfd0b2fd
Source dataset
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08828401B2

Reaction notes

Loading…

On this pageParticipantsProcedureWorkupSources & evidenceReaction notes