Triphenylphosphine → HCID 66709235, compound

HRID 1056619Notes

Reaction equation

HRID 1056619 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:16]=[C:15]2[C:10]=1[CH2:11][C@@H:12](O)[C@H:13]([C:27]1[CH:32]=[C:31]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:30]([O:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[C:29]([O:49][CH2:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[CH:28]=1)[O:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/[N:82]=N/C(OCC)=O)=O.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>C1COCC1.O.CCOC(C)=O>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:16]=[C:15]2[C:10]=1[CH2:11][C@H:12]([NH2:82])[C@H:13]([C:27]1[CH:32]=[C:31]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:30]([O:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[C:29]([O:49][CH2:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[CH:28]=1)[O:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 199401P,P-Diphenylphosphinic azideHCID 5462977Diethyl azodicarboxylateHCID 11193526HCID 11193526, compound

Product 1

HCID 66709235HCID 66709235, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (±)-trans-5,7-bis-benzyloxy-2-[3,4,5-tris(benzyloxy)phenyl]chroman-3-ol ((±)-1) (152.6 mg, 0.2 mmol) in THF (8.0 mL) was added triphenylphosphine (262.3 mg, 1.0 mmol), diethylazodicarboxylate (174.2 mg, 1.0 mmol) and diphenylphosphoryl azide (269.7 mg, 0.98 mmol) at room temperature. The solution was stirred at room temperature for 2 hours. EtOAc (20 mL) and H2O (10 mL) were added and stirred for an additional 10 minutes. The layers were separated and the aqueous layer was extracted with EtOAc (4×50 mL). The combined organic phase was washed with brine (15 mL) and dried over anhydrous Na2SO4. The solution was concentrated by rotary evaporator and vacuum drying to give the crude product which was purified by silica gel chromatography (C6H6/EtOAc=100/1) to afford the mixture of desired product and the elimination by-product (ratio is about 1/1). This mixture was dissolved in THF (8.0 mL), after which triphenylphosphine (85 mg) and H2O (65 mg) were added. The solution was refluxed overnight followed by addition of H2O (180 mg) and then refluxed for 3 hours. The solution was concentrated by rotary evaporator and vacuum drying to give the residue which was purified by silica gel chromatography (C6H6/EtOAc=5/1) to afford pure product 42 mg (28%) of (±)-2 as a white solid. 1H NMR: 300 MHz, CDCl3), 7.36 (m, 25 H), 6.74 (s, 2 H), 6.29 (s, 2 H), 5.16 (s, 4 H), 5.09 (s, 2 H), 5.04 (s, 4 H), 4.95 (s, 1 H), 3.34 (m, 1 H), 2.99 (dd, J=16.8, 5.2, 1 H), 2.86 (dd, J=16.8, 1.9, 1 H), 1.06 (s, br, 2 H). 13C NMR: (75.5 MHz, CDCl3), 158.47, 158.17, 154.86, 152.61, 137.79, 137.65, 136.85, 136.83, 136.74, 134.47, 128.46, 128.44, 128.37, 128.34, 128.19, 128.02, 127.86, 127.76, 127.72, 127.68, 127.41, 127.39, 127.04, 105.72, 101.44, 94.50, 93.83, 78.93, 75.16, 71.24, 70.08, 69.86, 48.27, 28.32. By employing the same procedure as described above, and starting from the appropriate enantiomer of 1, (−)-[2R,3R]-5,7-bis-benzyloxy-2-(3,4,5-tris-benzyloxyphenyl)chroman-3-yl-amine ((−)-2), [α]D=−14.6 (c=3.0, CHCl3) and (+)-[2S, 3S]-5,7-bis-benzyloxy-2-(3,4,5-tris-benzyloxyphenyl)chroman-3-yl-amine ((+)-2), [α]D=16.8 (c=3.5, CHCl3) were prepared with identical NMR spectra as (±)-2.

Workup

  1. stirringstirred for an additional 10 minutes
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (4×50 mL)
  4. washThe combined organic phase was washed with brine (15 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationThe solution was concentrated by rotary evaporator and vacuum
  7. customdrying
  8. customto give the crude product which
  9. customwas purified by silica gel chromatography (C6H6/EtOAc=100/1)
  10. customto afford

Sources & evidence

ORD record
ord-5bc471b7ab8b47bcbf5987dce49949c1
Source dataset
uspto-grants-2016_07
Patent number
US09399631B2

Reaction notes

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