Hydrochloric Acid → HCID 86702910, compound

HRID 1427885Notes

Reaction equation

HRID 1427885 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[C:21]([CH:22]4[CH2:24][CH2:23]4)=[CH:20][C:16]([C:17]([OH:19])=O)=[C:15]([F:25])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.FC(F)(F)C([O:30][CH2:31][CH2:32][CH2:33][NH:34][S:35](=[O:38])(=[O:37])[NH2:36])=O.C(=O)([O-])[O-].[Na+].[Na+].Cl>ClCCl.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[C:1]12([CH2:11][O:12][C:13]3[C:21]([CH:22]4[CH2:23][CH2:24]4)=[CH:20][C:16]([C:17]([NH:36][S:35](=[O:38])(=[O:37])[NH:34][CH2:33][CH2:32][CH2:31][OH:30])=[O:19])=[C:15]([F:25])[CH:14]=3)[CH2:8][CH:7]3[CH2:9][CH:3]([CH2:4][CH:5]([CH2:6]3)[CH2:10]1)[CH2:2]2

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 867028614-(Adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoic acidHCID 86702911HCID 86702911, compound

Product 1

HCID 86702910HCID 86702910, compoundYield 27%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 4-(adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoic acid (0.30 g, 0.87 mmol) in dichloromethane (15 mL) were added N-(3-dimethyl-aminopropyl)-N′-ethylcarbodiimide hydrochloride (0.38 g, 2.00 mmol) and 4-(dimethylamino)pyridine (0.25 g, 2.00 mmol). The reaction stirred at ambient temperature for 10 min, 3-(sulfamoylamino)propyl 2,2,2-trifluoroacetate (0.50 g, 2.00 mmol) was added and stirring continued at ambient temperature for 72 h. sodium carbonate solution (3M, 10 mL) was added and stirred at ambient temperature for 4 h, aqueous hydrochloric acid (3N) were added to pH=1 and diluted with ethyl acetate (200 mL), washed with water and brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by reversed-phase column chromatography afforded the title compound as colorless solid (0.11 g, 27%): 1H NMR (300 MHz, DMSO-d6) δ 11.50 (s, 1H), 7.66 (br s, 1H), 7.10 (d, J=8.3 Hz, 1H), 6.90 (d, J=12.9 Hz, 1H), 4.45 (t, J=5.0 Hz, 1H), 3.63 (s, 2H), 3.43-3.37 (m, 2H), 3.00-2.93 (m, 2H), 2.07-1.99 (m, 4H), 1.75-1.56 (m, 14H), 0.93-0.87 (m, 2H), 0.69-0.64 (m, 2H); MS (ES+) m/z 481.2 (M+1); MS (ES−) m/z 479.3 (M−1).

Workup

  1. stirringstirring
  2. waitcontinued at ambient temperature for 72 h.
  3. stirringstirred at ambient temperature for 4 h
  4. washwashed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by reversed-phase column chromatography

Sources & evidence

ORD record
ord-985b6709a8084fa19651336a88cbec6c
Source dataset
uspto-grants-2015_01
Patent number
US08933236B2

Reaction notes

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