Triethylamine → HCID 117873680, compound

HRID 517395Notes

Reaction equation

HRID 517395 reaction equation
[F:1][C:2]([F:28])([CH2:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)/[CH:3]=[CH:4]/[C@@H:5]1[C@@H:17]2[C@@H:8]([O:9][C:10](=[O:18])[CH2:11][CH2:12][CH2:13][CH:14]=[CH:15][CH2:16]2)[CH2:7][C@H:6]1[OH:19].C(N(CC)CC)C.[C:36]1([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH:41]=[CH:40][C:39]([C:42](Cl)=[O:43])=[CH:38][CH:37]=1.C(=O)(O)[O-].[Na+]>C1COCC1.CN(C)C1C=CN=CC=1>[C:45]1([C:36]2[CH:37]=[CH:38][C:39]([C:42]([O:19][C@@H:6]3[CH2:7][C@@H:8]4[O:9][C:10](=[O:18])[CH2:11][CH2:12][CH2:13][CH:14]=[CH:15][CH2:16][C@@H:17]4[C@H:5]3/[CH:4]=[CH:3]/[C:2]([F:1])([F:28])[CH2:20][O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:43])=[CH:40][CH:41]=2)[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 841514-Phenylbenzoyl chlorideHCID 516892Sodium BicarbonateHCID 70805938HCID 70805938, compound

Product 1

HCID 117873680HCID 117873680, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (8aR,9R,10R,11aS,Z)-9-((E)-3,3-difluoro-4-phenoxybut-1-en-1-yl)-10-hydroxy-4,5,8,8a,9,10,11,11a-octahydrocyclopenta[b]oxecin-2(3H)-one (20.0 g, from Example 34) in THF (200 mL) was treated with triethylamine (20.6 g, 0.20 mol), 4-(dimethylamino)pyridine (0.62 g, 5.09 mmol) and biphenyl-4-carbonyl chloride (33.0 g, 0.15 mol). This mixture was then stirred for 18 hr at room temperature under an atmosphere of nitrogen. Saturated aqueous solution of sodium bicarbonate (200 mL) was poured into the reaction mixture and the resulting mixture was stirred for 5 minutes. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (400 mL). The combined organic layers were dried over magnesium sulfate, the solid was filtered off and filtrate was concentrated under reduced pressure to give 40.0 g of crude product. The crude product was purified by column chromatography and then concentrated under reduced pressure to provide 20.0 g of the title compound (69.0% yield). The residue was crystallized from methanol to give white crystalline compound (mp 105˜109° C.). The x-ray powder diffraction pattern of crystalline title compound has characteristic peaks expressed in degrees 2θ at approximately 5.0, 6.2, 7.6, 9.5, 10.1, 11.5, 12.6, 13.7, 15.2, 18.0, 19.4, 21.2, 23.1, 23.6, 24.4, 25.7, 28.0, 37.9, 44.1.

Workup

  1. stirringthe resulting mixture was stirred for 5 minutes
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (400 mL)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationthe solid was filtered off
  6. concentrationfiltrate was concentrated under reduced pressure
  7. customto give 40.0 g of crude product
  8. customThe crude product was purified by column chromatography
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a4c4101f77644fadaf9137439f943bbf
Source dataset
uspto-grants-2015_08
Patent number
US09115109B2

Reaction notes

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