Hydrochloric Acid → HCID 178523967, compound

HRID 1265237Notes

Reaction equation

HRID 1265237 reaction equation
CC1C(C([C:18]2[CH:27]=[CH:26][C:21]([C:22](=[N:24][OH:25])[OH:23])=[CH:20][CH:19]=2)=O)=CC2C(C)(C)CCC(C)(C)C=2C=1.[H-].[Na+].[CH2:30](Br)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[NH4+].[Cl-].Cl>C1COCC1.CN1C(=O)N(C)CCC1>[CH2:30]([O:25][N:24]=[C:22]([OH:23])[C:21]1[CH:20]=[CH:19][CH:18]=[CH:27][CH:26]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 178421837HCID 178421837, compound

Product 1

HCID 178523967HCID 178523967, compoundYield 251%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

4-[(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl]benzoic acid (4.41 g, 12.6 mmol) in EtOH (10 mL) and pyridine (15.3 mL) was treated with hydroxylamine hydrochloride (4.38 g, 63 mmol), and the mixture was heated at reflux. After 6 h, the mixture was cooled to room temperature and the ethanol was removed in vacuo. The residue was taken-up in water and the aqueous layer was adjusted to pH=4.5 with 1 M aqueous HCl. The aqueous solution was extracted with EtOAc, 3×. The organic layer were combined and washed with water (2×) and brine. The organic solution was dried (NaSO4), filtered, and concentrated. Recrystallization (CH2Cl2/hexanes) gave 4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl]benzoic acid oximate 4.05 g (88%) as a white solid: mp 204-209° C. (d); 1H NMR (CDCl3/d-4MeOH) δ7.99 (½ABq, J=8.4 Hz, 2H, ArH), 7.53 (½ABq, J=8.4 Hz, 2H, ArH), 7.20 (s, 1H, ArH), 6.99 (s, 1H, ArH), 2.11 (s, 3H, CH3), 1.69 (s, 4H, 2CH2), 1.32 (s, 6H, 2CH3), 1.22 (s, 6H, 2CH3); HRMS: 366.2060 (MH+). A solution of 4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl]benzoic acid oxime (100 mg, 0.27 mmol) in THF (0.3 mL) and DMPU (0.3 mL) was added at 0° C. to a suspension of NaH (20 mg, 0.82 mmol) in THF (1.0 mL). The suspension was allowed to warm to room temperature was stirring over 30 minutes, then a solution of benzyl bromide (71 mL, 0.82 mmol) was added. The solution was allowed to warm to room temperature and stirred for 12 h. Aqueous, saturated NH4Cl (5.0 mL) was added and the aqueous layer was adjusted to pH=4-5 with 1 M aqueous HCl. The aqueous solution was extracted with EtOAc, 3×. The organic layers were combined and washed with water (2×) and brine. The organic solution was dried (Na2SO4), filtered, and concentrated to give a white solid. Purification by radial chromatography (10:1=hexanes: EtOAc) gave 4-[3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl]benzoic acid O-benzyloxime (105) 154 mg (61%) as a white solid: mp 169-172° C.; IR (neat) 2961 m, 2926 m 1691 s, 1420 w, 1285 w, 1016 w cm−1; 1H NMR (400 MHz, CDCl3) δ8.03 (½ABq, J=8.5 Hz, 2H, ArH), 7.55 (½ABq, J=8.5 Hz, 2H, ArH), 7.31 (m, 5H, ArH), 7.15 (s, 1H, ArH), 6.96 (s, 1H, ArH), 5.25 (s, 2H, OCH2) 2.00 (s, 3H, Ar—CH3), 1.69 (s, 4H, 2CH2), 1.31 (s, 6H, 2CH3), 1.22 (s, 6H, 2CH3); 13C NMR (100.8 MHz, CDCl3) δ171.7, 156.6, 145.3, 142.2, 141.4, 138.2, 132.5, 130.2, 130.1, 129.4, 128.2, 128.1, 127.9, 127.6, 127.0, 126.2, 35.2, 35.1, 34.1, 33.9, 31.9, 19.4; MS (FAB) m/e 4.56 (MH+); HRMS (FAB, MH+) Calcd for C30H33NO3: 456.2539 Found: 456.2526.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 12 h
  3. extractionThe aqueous solution was extracted with EtOAc, 3×
  4. washwashed with water (2×) and brine
  5. dry with materialThe organic solution was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a white solid
  9. customPurification by radial chromatography (10:1=hexanes: EtOAc)

Sources & evidence

ORD record
ord-bc989bf6e7f74c3fb23ec8d2e679b8a9
Source dataset
uspto-grants-2003_04
Patent number
US06545049B1

Reaction notes

Loading…