Tetrahydrofuran → N-(9-fluorenylmethoxycarbonyl)-O-(4,4-bis(diethylphosphoryl)butyl)-L-tyrosine

HRID 39268Notes

Reaction equation

HRID 39268 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:28]([OH:30])=[O:29])[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=3)=[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.C1C=[CH:35][C:34]([P:37]([C:44]2[CH:49]=[CH:48][CH:47]=CC=2)[C:38]2[CH:43]=CC=CC=2)=CC=1.N(C(O[CH:61]([CH3:63])C)=O)=NC(OC(C)C)=O.CC[O:66][P:67](OCC)([CH:69](P(OCC)(OCC)=O)[CH2:70]CCO)=O.C1C[O:88]CC1>>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:28]([OH:30])=[O:29])[CH2:20][C:21]3[CH:22]=[CH:23][C:24]([O:27][CH2:47][CH2:48][CH2:49][CH:44]([P:37]([CH2:34][CH3:35])([CH2:38][CH3:43])=[O:88])[P:67]([CH2:61][CH3:63])([CH2:69][CH3:70])=[O:66])=[CH:25][CH:26]=3)=[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

Participants

6

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 6957986(2S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-hydroxyphenyl)propanoic acidHCID 153967034,4-Bis(Diethoxyphosphoryl)butan-1-ol

Product 1

HCID 86762026N-(9-fluorenylmethoxycarbonyl)-O-(4,4-bis(diethylphosphoryl)butyl)-L-tyrosineYield 43%

Procedure

A solution of 83 (664 mg, 1.44 mmol) and PPh3 (454 mg, 1.73 mmol) in THF (20 mL) was cooled in an ice-bath followed by the addition of diisopropyl azodicarboxylate (336 mg, 1.74 mmol). After a further 10 min a solution of 81 (500 mg, 1.44 mmol) in THF (5 mL) was added and the resulting solution was stirred while warming to room temperature overnight. The solvent was removed at reduced pressure and the crude material was purified by silica gel chromatography (0 to 10% methanol in ethyl acetate over 10 column volumes then 10 to 20% over 5 column volumes) using a Biotage Horizon™ apparatus resulting in the colourless liquid 84 (491 mg, 43%): 1H NMR (400 MHz, CDCl3) δ 1.33 (t, J=7.1, 6H), 1.34 (t, J=7.1, 6H), 1.43 (s, 9H), 2.04-2.18 (m, 4H), 2.37 (tt, J=6.3, 24.2, 1H), 2.98-3.07 (m, 2H), 3.92 (t, J=5.8, 2H), 4.14-4.22 (m, 8H), 4.33 (dd, J=7.1, 10.4, 1H), 4.43 (dd, J=7.2, 10.5, 1H), 4.50 (dd, J=6.0, 8.4, 1H), 5.24, (d, J=8.1, 1H), 6.78 (d, J=8.5, 2H), 7.04 (d, J=8.4, 2H), 7.28-7.33 (m, 2H), 7.40 (t, J=7.6, 2H), 7.77 (d, J=7.6, 2H): 31P (162 MHz, CDCl3) δ 24.74 (s, 2P).

Workup

  1. customThe solvent was removed at reduced pressure
  2. customthe crude material was purified by silica gel chromatography (0 to 10% methanol in ethyl acetate over 10 column volumes

Sources & evidence

ORD record
ord-25c6d1d1a7234f55a4c27f12923f8b3f
Source dataset
uspto-grants-2013_09
Patent number
US08524691B2

Reaction notes

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