Triphenylphosphine → HCID 86728164, compound

HRID 627747Notes

Reaction equation

HRID 627747 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]3[O:44][C@@H:43]([CH3:45])[CH2:42][C@H:18]4[S:19](=[O:41])(=[O:40])[C:20]([CH3:39])([CH3:38])[C:21]([N:23]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[N:22][C@:17]4([CH3:46])[C:15]=3[CH:16]=2)=[O:9])=[N:6][CH:7]=1.[O:47]1[CH:51]=[CH:50][N:49]=[C:48]1[CH2:52]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[CH3:38][C:20]1([CH3:39])[S:19](=[O:41])(=[O:40])[C@@H:18]2[CH2:42][C@H:43]([CH3:45])[O:44][C:14]3[CH:13]=[CH:12][C:11]([NH:10][C:8]([C:5]4[CH:4]=[CH:3][C:2]([O:1][CH2:52][C:48]5[O:47][CH:51]=[CH:50][N:49]=5)=[CH:7][N:6]=4)=[O:9])=[CH:16][C:15]=3[C@@:17]2([CH3:46])[N:22]=[C:21]1[N:23]([C:24]([O:25][C:26]([CH3:29])([CH3:27])[CH3:28])=[O:30])[C:31](=[O:32])[O:33][C:34]([CH3:35])([CH3:36])[CH3:37]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 14786610(1,3-Oxazol-2-yl)methanolHCID 86728165HCID 86728165, compound

Product 1

HCID 86728164HCID 86728164, compoundYield 21.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 0° C. solution of tert-butyl N-[(4aR,6S,11bR)-10-[(5-hydroxypyridine-2-carbonyl)amino]-3,3,6,11b-tetramethyl-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (80 mg, 0.121 mmol), 2-oxazolemethanol (0.096 mL, 1.214 mmol) and triphenylphosphine (96 mg, 0.364 mmol) in THF (3 mL) was added diisopropyl azodicarboxylate (0.072 mL, 0.364 mmol) dropwise. The reaction was stirred at ambient temperature for 16 h. The reaction mixture was partitioned between water and ethyl acetate and the organic layer was concentrated. The crude product was purified by silica gel column chromatography, eluting with 20-100% ethyl acetate in heptane, to provide tert-butyl N-[(4aR,6S,11bR)-3,3,6,11b-tetramethyl-10-[[5-(oxazol-2-ylmethoxy)pyridine-2-carbonyl]amino]-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (19 mg, 0.026 mmol, 21.15% yield) as a colorless oil. MS m/z=762.0 (M+Na).

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. concentrationthe organic layer was concentrated
  3. customThe crude product was purified by silica gel column chromatography
  4. washeluting with 20-100% ethyl acetate in heptane

Sources & evidence

ORD record
ord-490c3c1082ec42fba50080bab966e621
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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