4-Methylmorpholine → HCID 86748804, compound

HRID 1648117Notes

Reaction equation

HRID 1648117 reaction equation
C(OC([NH:8][C@H:9]([C:13]([NH:15][C@H:16]([C:18]([NH:20][CH:21]1[CH:25]([O:26]CC2C=CC=CC=2)[O:24][C:23](=[O:34])[CH2:22]1)=[O:19])[CH3:17])=[O:14])[CH:10]([CH3:12])[CH3:11])=O)(C)(C)C.O[C:36]1[CH:41]=[CH:40][C:39]([CH2:42][CH2:43][C:44]([OH:46])=O)=[CH:38][CH:37]=1.OC1C2N=NNC=2C=CC=1.CN1CCOCC1.C(N=C=NCCCN(C)C)C>FC(F)(F)C(O)=O.C(OCC)(=O)C.CN(C)C=O>[C:39]1([CH2:42][CH2:43][C:44]([NH:8][C@H:9]([C:13]([NH:15][C@H:16]([C:18]([NH:20][CH:21]([CH:25]=[O:26])[CH2:22][C:23]([OH:34])=[O:24])=[O:19])[CH3:17])=[O:14])[CH:10]([CH3:11])[CH3:12])=[O:46])[CH:38]=[CH:37][CH:36]=[CH:41][CH:40]=1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 103943-(4-Hydroxyphenyl)propionic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 70043135HCID 70043135, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 86748804HCID 86748804, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6422Trifluoroacetic acidSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-(Tert-butoxycarbonyl-valinyl-alaninyl)-4-amino-5-benzyloxy-2-oxotetrahydrofuran (590.4 mg) was dissolved in 15 mL of trifluoroacetic acid, aged for 15 minutes, and concentrated. The residue was dissolved in methanol, diluted with toluene and concentrated to give a colorless solid. To 202.6 mg of this solid was added 3-(4-hydroxyphenyl)-propionic acid (137 mg, 0.8245 mmol), hydroxybenzotriazole (111 mg, 0.8245 mmol), dimethyl formamide (3 mL), and 4-methylmorpholine (45 μL, 0.4122 mmol). Ethyl dimethylaminopropyl carbodiimide (83 mg, 0.433 mmol) was added and the mixture stirred for 16 hours at ambient temperature. The mixture was diluted with ethyl acetate and washed three times with 2N hydrochloric acid, and twice with dilute sodium bicarbonate. The organics were dried over sodium sulfate, filtered, and concentrated to give the title compound as a mixture of two diastereomers: 1H NMR (400 MHz, CD3OD) δ7.4-7.2 (m, 5H, Ar--H), 7.01 (2d's, 2H, Ar--H), 6.66 (d, 2H, Ar--H), 4.9-4.6 (m, 2.5H, CH2Ph, CHN), 4.4-4.2 (m, 1.5H, CHN), 4.08 (d, 0.5H, J=7.43 Hz, CHN), 4.02 (d, 0.5H, J=7.15 Hz, CHH, 3.03 (dd, 0.5H, J=8.25, 18.31 Hz, CHHCO2), 2.9-2.7 (m, 2.5H, CHHCO2, CH2CON), 2.60 (dd, 0.5H, J=10.19, 17.29 Hz, CHHCO2), 2.55-2.45 (m, 2.5H, CHHCO2, CH2CH2 p--HOPh), 1.97 (m, 1H, CH(CH3)2), 1.32 (d, 1.5H, J=7.14 Hz, CHCH3), 1.26 (d, 1.5H, J=7.14 Hz, CHCH3), 0.9-0.8 (m, 6H, CH(CH3)2). ##STR35## N-(3-Phenylpropionyl-valinyl-alaninyl)-4-amino-5-benzyloxy-2-oxotetrahydrofuran

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in methanol
  3. additiondiluted with toluene
  4. concentrationconcentrated
  5. customto give a colorless solid
  6. washwashed three times with 2N hydrochloric acid
  7. dry with materialThe organics were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-9f39300c4ce2468396688543e7f87b4d
Source dataset
uspto-grants-1995_07
Patent number
US05434248

Reaction notes

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