4-Methylmorpholine → HCID 22942158, compound

HRID 362144

Reaction equation

HRID 362144 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:24](O)=[O:25])[CH2:20][CH:21]([CH3:23])[CH3:22])=[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.CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:42][CH:43]([B:46]1[O:50][C:49]([CH2:52][CH2:53][CH:54]([CH3:63])[CH2:55][C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])([CH3:51])[C:48]([CH3:65])([CH3:64])[O:47]1)[CH2:44][CH3:45]>ClCCl>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:24]([NH:42][CH:43]([B:46]3[O:50][C:49]([CH2:52][CH2:53][CH:54]([CH3:63])[CH2:55][C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])([CH3:51])[C:48]([CH3:64])([CH3:65])[O:47]3)[CH2:44][CH3:45])=[O:25])[CH2:20][CH:21]([CH3:23])[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

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 1549133Fmoc-leucineHCID 22619085Tert-butyl 5-[2-(1(rs)-aminopropyl)-4(rs),5,5-trimethyl-1,3,2-dioxaborolan-4-yl]-3(rs)-methylvalerate

Product 1

HCID 22942158HCID 22942158, compoundYield 58.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

0.5 g (1.42 mmol) of N-[(9-fluorenyl)methoxycarbonyl]-L-leucine was dissolved in 7 ml of dichloromethane. 0.6 ml (5.7 mmol) of N-methylmorpholine was added and the solution was cooled to -10° C.under a nitrogen atmosphere. 0.22 ml (1.7 mmol) of isobutyl chloroformate was added and the solution was stirred for 7 minutes at -10° C. 1 g(2.13 mmol) of tert-butyl 5-[2-(1(RS)-aminopropyl)-4(RS),5,5-trimethyl-1,3,2-dioxaborolan-4-yl]-3(RS)-methylvalerate was added and the mixture was stirred at room temperature for 16 hours, then diluted with dichloromethane and extracted with 2M hydrochloric acid. The organic phase was extracted with 2M hydrochloric acid and saturated sodium hydrogen carbonate solution and then dried over anhydrous magnesium sulphate. After evaporation the residue was purified by chromatography on silica gel using ethyl acetate/hexane (1:2) for the elution. There was obtained 0.56 g of tert-butyl 5-[2-[1(RS)-[[N-[(9-fluorenyl)methoxycarbonyl]-L-leucyl]amino]propyl]-4(RS),5,5-trimethyl-1,3,2-dioxaborolan-4-yl]-3(RS)-methylvalerate as an oil; MS: m/e 677 [M+H]+.

Workup

  1. stirringthe mixture was stirred at room temperature for 16 hours
  2. extractionextracted with 2M hydrochloric acid
  3. extractionThe organic phase was extracted with 2M hydrochloric acid and saturated sodium hydrogen carbonate solution
  4. dry with materialdried over anhydrous magnesium sulphate
  5. customAfter evaporation the residue
  6. customwas purified by chromatography on silica gel
  7. washfor the elution

Sources & evidence

ORD record
ord-5d6c7882af50462ca0f6c31eab2df330
Source dataset
uspto-grants-1999_02
Patent number
US05866684

Linked notes

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