4-Methylmorpholine → 4-(tert-Butyl-dimethyl-silanyloxy)-3-({6-[(naphthalene-2-carbonyl)-amino]-5-oxo-1,2,3,5,6,7,10,10a-octahydro-pyrrolo[1,2-a]azocine-3-carbonyl}-amino)-butyric acid benzyl ester

HRID 1824442Notes

Reaction equation

HRID 1824442 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([NH:13][CH:14]1[C:21](=[O:22])[N:20]2[CH:23]([C:26](O)=[O:27])[CH2:24][CH2:25][CH:19]2[CH2:18][CH:17]=[CH:16][CH2:15]1)=[O:12].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[CH2:57]([O:64][C:65](=[O:78])[CH2:66][CH:67]([NH2:77])[CH2:68][O:69][Si:70]([C:73]([CH3:76])([CH3:75])[CH3:74])([CH3:72])[CH3:71])[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1>C1COCC1.O>[CH2:57]([O:64][C:65](=[O:78])[CH2:66][CH:67]([NH:77][C:26]([CH:23]1[N:20]2[C:21](=[O:22])[CH:14]([NH:13][C:11]([C:2]3[CH:3]=[CH:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH:1]=3)=[O:12])[CH2:15][CH:16]=[CH:17][CH2:18][CH:19]2[CH2:25][CH2:24]1)=[O:27])[CH2:68][O:69][Si:70]([C:73]([CH3:74])([CH3:75])[CH3:76])([CH3:72])[CH3:71])[C:58]1[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 23571419HCID 23571419, compoundHCID 69584313HCID 69584313, compound

Product 1

HCID 695844714-(tert-Butyl-dimethyl-silanyloxy)-3-({6-[(naphthalene-2-carbonyl)-amino]-5-oxo-1,2,3,5,6,7,10,10a-octahydro-pyrrolo[1,2-a]azocine-3-carbonyl}-amino)-butyric acid benzyl esterYield 67.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution containing 6-[(Naphthalene-2-carbonyl)-amino]-5-oxo-1,2,3,5,6,7,10,10a-octahydro-pyrrolo[1,2-a]azocine-3-carboxylic acid (425 mg, 1.12 mmol), EDCI (240 mg, 1.25 mmol), HOBt (170 mg, 1.25 mmol), and NMM (0.15 mL, 1.25 mmol) in THF (15 mL) is stirred at rt for 20 min. A solution of 3-Amino-4-(tert-butyl-dimethyl-silanyloxy)-butyric acid benzyl ester (400 mg, 1.25 mmol, prepared by methods outlined in Chem. Pharm. Bull. 1999, 47, 11–21) in 5 mL of THF is added and the solution is stirred at rt for 12 h. The solution is poured into water and the aqueous solution is extracted with EtOAc. The combined organic extracts are washed with saturated NaHCO3 and brine, dried (Na2SO4), filtered, concentrated, and purified by flash chromatography on silica gel (hexane/EtOAc) to yield 520 mg of desired product. 1H NMR (CDCl3) δ 8.33 (s, 1H), 7.88 (m, 4H), 7.56 (m, 3H), 7.36 (m, 4H), 7.14 (d, J=8.4 Hz, 1H), 5.86 (m, 1H), 5.75 (m, 1H), 5.46 (m, 1H), 5.13 (s, 2H), 4.63 (d, J=7.5 Hz, 1H), 4.40 (m, 1H), 5.75 (m, 1H), 5.46 (m, 1H), 5.13 (s, 2H), 4.63 (d, J=13.5 Hz, 1H), 2.94 (m, 1H), 2.75–2.56 (m, 2H), 2.37–2.21 (m, 2H), 2.10–1.70 (m, 3H), 0.93 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H).

Workup

  1. stirringthe solution is stirred at rt for 12 h
  2. extractionthe aqueous solution is extracted with EtOAc
  3. washThe combined organic extracts are washed with saturated NaHCO3 and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash chromatography on silica gel (hexane/EtOAc)

Sources & evidence

ORD record
ord-9dcb63321d254485af8e7f8c12454585
Source dataset
uspto-grants-2006_05
Patent number
US07041696B2

Reaction notes

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