HCID 86730049, compound → HCID 86730048, compound

HRID 516952Notes

Reaction equation

HRID 516952 reaction equation
[CH2:1]([C:7]1[CH2:16][CH2:15][C:14]2[CH:13]=[C:12]([C@H:17]3[CH2:26][CH2:25][C@@:19]4([NH:23][C:22](=[O:24])[O:21][CH2:20]4)[CH2:18]3)[CH:11]=[CH:10][C:9]=2[CH:8]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]>CO>[CH2:1]([CH:7]1[CH2:16][CH2:15][C:14]2[CH:13]=[C:12]([C@H:17]3[CH2:26][CH2:25][C@@:19]4([NH:23][C:22](=[O:24])[O:21][CH2:20]4)[CH2:18]3)[CH:11]=[CH:10][C:9]=2[CH2:8]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]

Participants

3

Reactant 1

HCID 86730049HCID 86730049, compound

Product 1

HCID 86730048HCID 86730048, compoundYield 83.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of (5R,7S)-7-(6-hexyl-7,8-dihydronaphthalen-2-yl)-3-oxa-1-azaspiro[4.4]nonan-2-one (2A, 760 mg, 2.15 mmol) and (−)-2,3-bis[(2R,5R)-2,5-dimethylphospholanyl]-N-[3,5-bis(trifluoromethyl)phenyl]maleicimide(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate (273 mg, 0.43 mmol) in MeOH (27 mL) was hydrogenated at 850 PSI for 1000 minutes using a 100 mL HEL autoclave. The reaction mixture was filtered and concentrated in vacuo. The crude material was purified on a silica gel cartridge (40 g) using an EtOAc/hexane gradient (0-100% EtOAc over 20 minutes) to afford 640 mg of (5R,7S)-7-(6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)-3-oxa-1-azaspiro[4.4]nonan-2-one in a 1:2 ratio of the two isomers. The desired major isomer was separated using a CHIRALPAK® AS-H column under SFC conditions (35% MeOH in CO2). Retention time=5.14 min. Recovered 400 mg of (5R,7S)-7-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)-3-oxa-1-azaspiro[4.4]nonan-2-one. 1H NMR (400 MHz, methanol-d4) δ 7.02-6.91 (m, 3H), 4.47-4.20 (m, 2H), 3.02 (tt, J=11.0, 7.2 Hz, 1H), 2.87-2.74 (m, 3H), 2.41-2.24 (m, 2H), 2.17-2.03 (m, 2H), 2.00-1.89 (m, 3H), 1.86-1.74 (m, 1H), 1.73-1.61 (m, 1H), 1.51-1.28 (m, 11H), 0.99-0.88 (m, 3H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated in vacuo
  3. customThe crude material was purified on a silica gel cartridge (40 g)
  4. customan EtOAc/hexane gradient (0-100% EtOAc over 20 minutes)

Sources & evidence

ORD record
ord-bc5d5a1bea724be8abd13681c290f5c7
Source dataset
uspto-grants-2015_08
Patent number
US09115054B2

Reaction notes

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