Sodium Hydroxide → HCID 58137321, compound

HRID 1424638Notes

Reaction equation

HRID 1424638 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:28]=1[C:9]1([CH2:14][CH2:13][N:12]([C:15]([O:17][CH:18]3[CH:25]4[CH2:26][CH:21]5[CH2:22][CH:23]([CH2:27][CH:19]3[CH2:20]5)[CH2:24]4)=[O:16])[CH2:11][CH2:10]1)[CH2:8][CH:7]2[CH2:29]C(O)=O.C1(P([N:47]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[OH-].[Na+]>C1COCC1>[NH2:47][CH2:29][CH:7]1[C:6]2[C:28](=[C:2]([Br:1])[CH:3]=[CH:4][CH:5]=2)[C:9]2([CH2:14][CH2:13][N:12]([C:15]([O:17][CH:18]3[CH:25]4[CH2:26][CH:21]5[CH2:22][CH:23]([CH2:27][CH:19]3[CH2:20]5)[CH2:24]4)=[O:16])[CH2:11][CH2:10]2)[CH2:8]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 199401P,P-Diphenylphosphinic azideHCID 25065430HCID 25065430, compound

Product 1

HCID 58137321HCID 58137321, compoundYield 4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 100-mL of flask was charged with (±)-2-(7-bromo-1′-((2-adamantyloxy)carbonyl)-2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)acetic acid (30 mg, 0.06 mmol) dissolved in THF (3 mL) and treated with TEA (2 mL). Then diphenylphosphoryl azide (18 mg, 0.066 mmol) was added dropwise slowly. The mixture was stirred for 3 h at rt. 1 N aq NaOH solution (3 mL) was added and the reaction mixture was reflux overnight. The solvent was removed in vacuo and the aqueous residue was extracted with CH2Cl2 (3×5 mL). The organic layers were combined, washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative HPLC to give (±)-2-adamantyl 3-(aminomethyl)-7-bromo-2,3-dihydrospiro[indene-1,4′-piperidine]-1′-carboxylate (1 mg, 4%). LC-MS Method 5 tR=1.175 min, m/z=475; 1H NMR (400 MHz, MeOD): δ=0.71-0.83 (m, 3H), 1.46-1.57 (m. 2H), 1.61-1.81 (m, 6H), 1.81-2.06 (m, 11H), 2.39-2.51 (m, 1H), 2.83-3.00 (m, 2H), 3.41-3.57 (m, 2H), 4.07-4.14 (m, 1H), 4.79 (m, 1H), 6.99-7.10 (m, 2H), 7.37 (m, 1H), 7.95-8.30 (s, 1H).

Workup

  1. temperaturethe reaction mixture was reflux overnight
  2. customThe solvent was removed in vacuo
  3. extractionthe aqueous residue was extracted with CH2Cl2 (3×5 mL)
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-12e59c15399b45a9bd35082cca9c3de0
Source dataset
uspto-grants-2015_01
Patent number
US08927715B2

Reaction notes

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