Trifluoroacetic acid → HCID 66870013, compound

HRID 1994374Notes

Reaction equation

HRID 1994374 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[C@H:16]([C:17](=[O:35])[NH:18][C@@H:19]([CH2:27][C:28]([O:30]C(C)(C)C)=[O:29])[CH:20]([O:24][CH2:25][CH3:26])OCC)[C@@H:15]2[CH2:36][C@H:12]1[CH2:13][CH2:14]2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClCCl.C(=O)(O)[O-].[Na+]>[CH2:1]([O:8][C:9]([N:11]1[C@H:16]([C:17](=[O:35])[NH:18][C@H:19]2[CH2:27][C:28](=[O:29])[O:30][C@H:20]2[O:24][CH2:25][CH3:26])[C@@H:15]2[CH2:36][C@H:12]1[CH2:13][CH2:14]2)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66870411HCID 66870411, compound

Product 1

HCID 66870013HCID 66870013, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (1R,3S,4S)-3-((S)-1-tert-Butoxycarbonylmethyl-2,2-diethoxy-ethylcarbamoyl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid benzyl ester (635 mg) in dichloromethane (3 ml) was cooled to 0° C. under nitrogen. Trifluoroacetic acid (0.7 ml) was then added and the mixture stirred at 0° C. for 15 minutes, then warmed to ambient temperature and stirred until the reaction was complete by TLC. The mixture was then diluted with dichloromethane (10 ml) and saturated aqueous sodium bicarbonate solution (14 ml). The organic phase was then removed and washed with 1:1 saturated aqueous sodium bicarbonate/brine (8 ml), dried (magnesium sulfate), filtered and concentrated under reduced pressure. This afforded the sub-title compound as a mixture of epimers at the ketal centre. The epimers were separated on silica gel, eluting with 30% 2-butanone/petrol. Syn-isomer (oil) (115 mg, 23%); 1H NMR (400 MHz, d-6 DMSO) δ 0.80-1.91 (10H, m), 2.35-2.79 (2H, m), 3.56 (1H, m), 3.66-3.80 (2H, m), 4.18 (1H, m), 4.59 (1H, m), 4.94-5.11 (2H, m), 5.53 (1H, d), 7.20-7.40 (5H, m), 8.18 (0.5H, d), 8.27 (0.5H, d); MS ES+403.31 (100%), ES−401.37 (15%); Anti-isomer (oil) (103 mg, 20%); 1H NMR (400 MHz, d-6 DMSO) δ 0.80-1.85 (10H, m), 2.25-2.60 (1H, m), 2.95 (1H, m), 3.42 (1H, m), 3.5-3.75 (2H, m), 4.88-5.15 (3H, m), 7.21-7.40 (5H, m), 8.50 (0.4H, d), 8.59 (0.6H, d).

Workup

  1. temperaturewarmed to ambient temperature
  2. stirringstirred until the reaction
  3. customThe organic phase was then removed
  4. washwashed with 1:1 saturated aqueous sodium bicarbonate/brine (8 ml)
  5. dry with materialdried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-44c3a7768e824001b99edf6274f359dc
Source dataset
uspto-grants-2010_01
Patent number
US07652153B2

Reaction notes

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