Diisopropylethylamine → 9H-fluoren-9-ylmethyl {2-[(4-{[(tert-butoxycarbonyl)amino]methyl}phenyl)amino]-2-oxoethyl}carbamate

HRID 1755201Notes

Reaction equation

HRID 1755201 reaction equation
[C:1](NCC(O)=O)([O:3][CH2:4][CH:5]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:2].C(N(CC)C(C)C)(C)C.[NH2:32][CH2:33][C:34]([NH:36][C:37]1[CH:51]=[CH:50][C:40]([CH2:41][NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[CH:39][CH:38]=1)=[O:35]>CN(C=O)C>[C:45]([O:44][C:43]([NH:42][CH2:41][C:40]1[CH:39]=[CH:38][C:37]([NH:36][C:34](=[O:35])[CH2:33][NH:32][C:1](=[O:2])[O:3][CH2:4][CH:5]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[C:11]3[C:6]2=[CH:7][CH:8]=[CH:9][CH:10]=3)=[CH:51][CH:50]=1)=[O:49])([CH3:46])([CH3:47])[CH3:48]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 93124Fmoc-Gly-OHHCID 86718402Tert-butyl [4-(glycylamino)benzyl]carbamate

Product 1

HCID 867184019H-fluoren-9-ylmethyl {2-[(4-{[(tert-butoxycarbonyl)amino]methyl}phenyl)amino]-2-oxoethyl}carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of Fmoc-Glycine (16 g, 54 mmol, 1.0 eq.) in dry DMF (160 mL) at 0° C. was added N,N-diisopropylethylamine (14 g, 108 mmol, 2.0 eq) and N N,N′,N′-Tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate (16 g, 54 mmol, 1.0 eq). The mixture was stirred at 0° C. for 30 min and a solution of tert-butyl [4-(glycylamino)benzyl]carbamate (12 g, 54 mmol, 1.0 eq.) in dry DMF (50 mL) was added. The mixture was stirred at room temperature overnight poured into ice water (400 mL) and extracted with EtOAc (400 mL×2). The organic layer was washed with brine (200 mL×2), dried over Na2SO4 and concentrated in vacuum. The residue was re-crystallized from EtOAc (200 mL) and petroleum ether (400 mL) to afford #B118 (18 g, 66.6%) as a white solid. 1H NMR (400 Hz, DMSO-d6): δ 9.93 (s, 1H), 7.91 (d, 2H), 7.75 (d, 2H), 7.61 (m, 1H), 7.52 (d, 2H), 7.43 (m, 2H), 7.36 (m, 3H), 7.18 (d, 3H), 4.32 (d, 2H), 4.26 (m, 1H), 4.07 (d, 2H), 3.80 (d, 2H), 1.39 (s, 9H)

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. extractionextracted with EtOAc (400 mL×2)
  3. washThe organic layer was washed with brine (200 mL×2)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuum
  6. customThe residue was re-crystallized from EtOAc (200 mL) and petroleum ether (400 mL)
  7. customto afford #B118 (18 g, 66.6%) as a white solid

Sources & evidence

ORD record
ord-c8b3a153a0b54dc0960b8e7dd14fc917
Source dataset
uspto-grants-2015_10
Patent number
US09169264B2

Reaction notes

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