Benzoyl chloride → HCID 69673097, compound

HRID 2276351Notes

Reaction equation

HRID 2276351 reaction equation
[NH2:1][C:2]1[C:3]([C:12]([OH:14])=[O:13])=[CH:4][C:5]2[CH2:6][CH2:7][CH2:8][CH2:9][C:10]=2[CH:11]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:21](Cl)(=O)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>>[C:22]1([C:21]2[O:13][C:12](=[O:14])[C:3]3[CH:4]=[C:5]4[C:10]([CH2:9][CH2:8][CH2:7][CH2:6]4)=[CH:11][C:2]=3[N:1]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

4

Reactant 3

HCID 7412Benzoyl chlorideHCID 10340Sodium CarbonateHCID 137397303-Amino-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid

Product 1

HCID 69673097HCID 69673097, compoundYield 44.5%

Procedure

2-Phenyl-6,7,8,9-tetrahydro-naphtho[2,3-d][1,3]oxazin-4-one was prepared by a modification of the route described in Okabe, M. and Sun, R. C.; Tetrahedron 1995, 51(7), 1861-1866. A 100 mL flask was charged with 3-amino-5,6,7,8-tetrahydro-napthalene-2-carboxylic acid, prepared in 36% yield as described in WO 2007/081572 (360 mg, 1.88 mmol) and sodium carbonate (399 mg, 3.77 mmol) and was then evacuated and backfilled with dry nitrogen gas twice before the addition of anhydrous tetrahydrofuran (50 mL). Cooled in an ice bath and added benzoyl chloride (662 mg, 4.71 mmol) and allowed to warm to ambient temperature overnight with stirring. Evaporated in vacuo and partitioned between ethyl acetate and water (20 mL each). Organic fraction was separated, dried with a hydrophobic frit, evaporated onto silica gel, and chromatographed using ISCO Companion with a Redisep silica gel 12 g cartridge and a gradient of heptane and ethyl acetate (0% to 50%). Impure fractions were combined and crystallized from refluxing heptane solution (˜100 mL). Pure material from the column was combined with material obtained by crystallization to give 2-phenyl-6,7,8,9-tetrahydro-naphtho[2,3-d][1,3]oxazin-4-one as a white solid 232.3 mg (44.5% Yield) LCMS (5 min acidic) 3.19 min 100% pure by ELSD, 36-100% pure by UV, ES+/AP+ 278. HNMR (CDCl3) >95% Pure 8.31-8.29 (m, 2H), 7.96 (s, 1H), 7.57-7.47 (m, 3H), 7.41 (s, 1H), 2.95-2.92 (m, 4H), 1.89-1.86 (m, 4H).

Workup

  1. custom2-Phenyl-6,7,8,9-tetrahydro-naphtho[2,3-d][1,3]oxazin-4-one was prepared by a modification of the route
  2. customprepared in 36% yield
  3. customwas then evacuated
  4. additionbackfilled with dry nitrogen gas twice before the addition of anhydrous tetrahydrofuran (50 mL)
  5. temperatureCooled in an ice bath
  6. customEvaporated in vacuo
  7. custompartitioned between ethyl acetate and water (20 mL each)
  8. customOrganic fraction was separated
  9. customdried with a hydrophobic frit
  10. customevaporated onto silica gel
  11. customchromatographed
  12. customcrystallized
  13. temperaturefrom refluxing heptane solution (˜100 mL)
  14. customobtained by crystallization

Sources & evidence

ORD record
ord-0b2f399cfdd848c0975e1cc1d0281da8
Source dataset
uspto-grants-2015_09
Patent number
US09132129B2

Reaction notes

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