Methanol → HCID 69942605, compound

HRID 428325Notes

Reaction equation

HRID 428325 reaction equation
[ClH:1].[CH:2]([N:5]([CH:27]([CH3:29])[CH3:28])[CH2:6][CH2:7][C@@H:8]([C:15]1[CH:20]=[C:19]([CH2:21][CH2:22]C(=O)N)[CH:18]=[CH:17][C:16]=1[OH:26])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([CH3:4])[CH3:3].[OH-:30].[K+].[CH3:32][OH:33]>C(O)C.O>[ClH:1].[CH:27]([N:5]([CH:2]([CH3:3])[CH3:4])[CH2:6][CH2:7][C@@H:8]([C:15]1[CH:20]=[C:19]([CH2:21][CH2:22][C:32]([OH:33])=[O:30])[CH:18]=[CH:17][C:16]=1[OH:26])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([CH3:29])[CH3:28]

Participants

6

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 69943082HCID 69943082, compound

Product 1

HCID 69942605HCID 69942605, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (R)-N,N-diisopropyl-3-[5-(2-carbamoylethyl)-2-hydroxyphenyl]-3-phenylpropanamine (obtained in Example 25), (0.50 g, 1.31 mmol) in ethanol (15 mL) and H2O (10 mL) was added KOH (3.75 g, 66.8 mmol). The mixture was stirred overnight at 100° C. The solvent was evaporated and the residue redissolved in H2O and washed with diethyl ether. The aqueous layer was acidified with conc. HCl and the precipitate was collected by filtration and washed with 2 M HCl. The product was fractionated on a reversed-phase PEP RPC HR 30/26 (Pharmacia Biotech AB, Sweden) column using a gradient of 20-60% acetonitrile with 0.1% TFA. Fractions were pooled and hydrochloric acid (2 mL, conc.) was added and the solvent was evaporated. The residue was crystallised from methanol-diethyl ether to give 0.37 g (0.96 mmol, 74%); 1H NMR (CD3OD) δ1.28 (m, 12H), 2.48 (m, 4H), 2.76 (t, 2H), 3.04 (t, 2H), 3.67 (m, 2H), 4.39 (t, 1H), 6.72 (d, 1H), 6.92 (d, 1H), 7.00 (s, 1H), 7.19 (t, 1H), 7.32 (m, 4H); mp. 205-207° C.; [α]D +3.7° (c=1.0, methanol). Anal. (C24H33NO3*1.0HCl) C, H, N.

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue redissolved in H2O
  3. washwashed with diethyl ether
  4. filtrationthe precipitate was collected by filtration
  5. washwashed with 2 M HCl
  6. additionhydrochloric acid (2 mL, conc.) was added
  7. customthe solvent was evaporated
  8. customThe residue was crystallised from methanol-diethyl ether
  9. customto give 0.37 g (0.96 mmol, 74%)

Sources & evidence

ORD record
ord-aad4130f9c324a4babb50eecb8953b1f
Source dataset
uspto-grants-2001_11
Patent number
US06313132B1

Reaction notes

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