4-Methylmorpholine → HCID 67430248, compound

HRID 1660707Notes

Reaction equation

HRID 1660707 reaction equation
[NH2:1][CH:2]([CH3:21])[CH:3]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:4][O:5][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.[C:39]([N:49]([CH3:63])[C@H:50]([C:60](O)=[O:61])[CH2:51][C:52]1[CH:57]=[CH:56][C:55]([O:58][CH3:59])=[CH:54][CH:53]=1)([O:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:40].C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl>[C:39]([N:49]([CH3:63])[C@H:50]([C:60]([NH:1][CH:2]([CH3:21])[CH:3]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:4][O:5][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7])=[O:61])[CH2:51][C:52]1[CH:57]=[CH:56][C:55]([O:58][CH3:59])=[CH:54][CH:53]=1)([O:41][CH2:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)=[O:40]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 11099982HCID 11099982, compoundHCID 72457689HCID 72457689, compound

Product 1

HCID 67430248HCID 67430248, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of amine 110 (20 mg, 0.062 mmol) in CH2Cl2 (1 mL), cooled to 0° C., NMM (7 μL, 0.069 mmol) and HOBt (25 mg, 0.18 mmol) were added. The solution was stirred at 0° C. for 15 minutes, and a solution of N-Cbz-N,O-dimethyltyrosine (21) (21 mg, 0.062 mmol) in CH2Cl2 (1 mL) was added. Finally a solution of DCC (14.2 mg, 0.069 mmol) in CH2Cl2 (1 mL) was added. The mixture was stirred 16 h at room temperature and filtered to remove the precipitate. The filtrate was diluted with CH2Cl2 (10 mL) and washed with 10% KHSO4 (10 mL), 5% NaHCO3 (10 mL) and NaCl (10 mL, sat), dried (Na2SO4), filtered, and concentrated. The crude oil was purified by column chromatography (silica gel, EtOAc/Hexanes 1/3) to yield 111 (26 mg, 70%) as a white foam. Rf 0.36 (AcOEt/Hexanes 1/3). [α]D20=−40.1 (c=0.5, CHCl3). 1H-NMR (500 MHz, CDCl3): 0.09 (s, 6H), 0.95 (s, 9H), 1.14-1.17 (m, 3H), 1.43 (s, 9H), 2.86 (s, 3H), 3.29-3.32 (m, 1H), 3.42-3.48 (m, 1H), 3.60-3.68 (m, 2H), 3.82 (s, 3H), 4.17-4.18 (m, 1H), 4.87-4.89 (m, 1H), 4.95-4.96 (m, 1H), 5.02-5.14 (m, 2H), 5.21-5.22 (m, 2H), 6.34-6.37 (m, 1H), 6.79-6.83 (m, 2H), 6.98-7.00 (m, 1H), 7.01-7.17 (m, 2H), 7.20-7.36 (m, 5H). 13C-NMR (125 MHz, CDCl3): −5.5, 17.9, 18.2, 25.8, 28.3, 33.2, 44.5, 55.12, 62.6, 67.3, 57.1, 66.1, 113.8, 127.5, 127.9, 128.4, 129.8, 158.2, 171.5. IR (neat) 3328.5, 2930.3, 2856.3, 2361.0, 2346.6, 2249.0, 1708.8, 1513.7, 1452.5, 1449.5. HRMS m/z cald for C34H53N5O7Na (M+Na): 666.3550 found 666.3571.

Workup

  1. stirringThe mixture was stirred 16 h at room temperature
  2. filtrationfiltered
  3. customto remove the precipitate
  4. additionThe filtrate was diluted with CH2Cl2 (10 mL)
  5. washwashed with 10% KHSO4 (10 mL), 5% NaHCO3 (10 mL) and NaCl (10 mL, sat)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude oil was purified by column chromatography (silica gel, EtOAc/Hexanes 1/3)

Sources & evidence

ORD record
ord-0501558037b24df4a79caf7bdb122b6b
Source dataset
uspto-grants-2011_10
Patent number
US08030279B2

Reaction notes

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