Water → HCID 86755443, compound

HRID 1420698Notes

Reaction equation

HRID 1420698 reaction equation
[BH4-].[Na+].[CH2:3]([N:12]1[CH2:38][CH2:37][CH2:36][C:14]2([O:18][CH2:17][CH:16]([C:19]3[CH:24]=[C:23]([N:25]4[CH:29]=[CH:28][N:27]=[C:26]4[C:30]([F:33])([F:32])[F:31])[CH:22]=[CH:21][C:20]=3[O:34][CH3:35])[CH2:15]2)[CH2:13]1)[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].O>C(O)C>[OH:5][CH:4]([C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)[CH2:3][N:12]1[CH2:38][CH2:37][CH2:36][C:14]2([O:18][CH2:17][CH:16]([C:19]3[CH:24]=[C:23]([N:25]4[CH:29]=[CH:28][N:27]=[C:26]4[C:30]([F:32])([F:33])[F:31])[CH:22]=[CH:21][C:20]=3[O:34][CH3:35])[CH2:15]2)[CH2:13]1

Participants

5

Reactant 3

HCID 962WaterHCID 4311764Sodium borohydrideHCID 86755444HCID 86755444, compound

Product 1

HCID 86755443HCID 86755443, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Sodium borohydride (12 mg, 0.32 mmol) was added to a solution of (±)-(3R*, 5R*)-7-phenacyl-3-(2-methoxy-5-(2-trifluoromethyl-1H-imidazol-1-yl)phenyl)-1-oxa-7-azaspiro[4,5]decane (105.9 mg, 0.212 mmol) in ethanol (2 ml) and the mixture stirred at room temperature for 4 hours. The mixture was poured into water (50 ml) and extracted with ethyl acetate (2×20 ml). The extracts were washed with brine (20 ml), combined, dried (MgSO4) and concentrated. The residue was purified by flash chromatography, eluting with 5% then 7.5% methanol in dichloromethane to give (±)-(3R*, 5R*, 12S*/R*)-7-(2-hydroxy-2-phenylehtyl)-3-(2-methoxy-5-(2-trifluoromethyl-1H-imidazol-1-yl)phenyl)-1-oxa-7-azaspiro[4,5]decane (86.0 mg, 81%). The free base was dissolved in ether and treated with oxalic acid (15.7 mg) in ether. The resulting precipitate was collected under suction, washed with ether and dried in vacuo to afford the title compound (75.1 mg); (Found: C, 58.89; H, 5.11; N, 6.87. C27H30F3N3O3. C2H2O4 requires C, 58.88; H, 5.45; N, 7.10%; δH (360 MHz, D2O) 1.72-2.37 (6H, m), 3.11 (2H, m), 3.34-3.96 (10H, m), 4.27 (1H, m), 5.25 (1H, m), 7.13 (1H, d, J 9.3 Hz, 3'-H), 7.22 (1H, br s, imidazole H), 7.36 (3H, m, ArH), 7.47 (5H, m, ArH); m/z (ES+) 502 ([M+H]+).

Workup

  1. extractionextracted with ethyl acetate (2×20 ml)
  2. washThe extracts were washed with brine (20 ml)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography
  6. washeluting with 5%

Sources & evidence

ORD record
ord-c5fa15999a5e46f2b6f73a7a8d97d573
Source dataset
uspto-grants-2000_06
Patent number
US06071928

Reaction notes

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