Hydrochloric Acid → HCID 68537029, compound

HRID 1991532Notes

Reaction equation

HRID 1991532 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]([NH:11][CH2:12][C@@H:13]([OH:32])[C@@H:14]([NH:24][C:25](=[O:31])OC(C)(C)C)[CH2:15][C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=2)([CH3:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.F[C:34](F)(F)[C:35]([OH:37])=O.[C:40](C1NC=CN=1)(=O)C.[ClH:48]>C(Cl)Cl.CCOCC>[ClH:48].[C:35]([O:32][C@H:13]([CH2:12][NH:11][C:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=1)([CH3:10])[CH3:9])[C@@H:14]([NH:24][C:25](=[O:31])[CH3:40])[CH2:15][C:16]1[CH:17]=[C:18]([F:23])[CH:19]=[C:20]([F:22])[CH:21]=1)(=[O:37])[CH3:34]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 5389722-AcetylimidazoleHCID 58909388HCID 58909388, compound

Product 1

HCID 68537029HCID 68537029, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To 365 mg (0.71 mmol) of tert-butyl (1S,2R)-3-{[1-(3-bromophenyl)-1-methylethyl]amino}-1(3,5-difluorobenzyl)-2-hydroxypropylcarbamate 30 in 2 mL of CH2Cl2 is added 1 mL of trifluoroacetic acid, and the mixture is stirred for 30 min. It is concentrated in vacuo, diluted with ethyl acetate, and washed with 10% Na2CO3 and then brine. The solution is dried over Na2SO4, filtered and concentrated to a colorless oil. This is dissolved in 3 mL of CH2Cl2 and 172 mg (1.56 mmol) of acetyl imidazole is added. After 2.5 h the mixture is concentrated and taken up in ethyl acetate and 1 N KH2PO4. The organic phase is washed with 1N KH2PO4, with brine, dried over Na2SO4, concentrated, and chromatographed over silica gel. Elution with 4% methanol (containing 1% of NH4OH) in CH2Cl2 affords a sticky solid. This is dissolved in ether and treated with ethereal HCl. Concentration afford 260 mg (0.49 mmol, 68%) of compound 31 as a white solid: 1H NMR (CDCl3+CD3OD drop) δ 7.79 (n m, 1H), 7.59 (m, 2H), 7.36 (t, J=8 Hz, 1H), 6.69-6.62 (m, 3H), 5.15 (m, 1H), 4.17 (m, 1H), 3.07 (d, J=12.5 Hz, 1H), 2.87-2.75 (m, 2H), 2.61 (dd, J=7, 13.5 Hz, 1H), 2.21 (s, 3H), 1.95 (s, 3H), 1.92 (s, 3H), 1.84 (s, 3H); IR (diffuse reflectance) 2985, 2958, 2940, 2755, 2738, 2730, 1749, 1645, 1628, 1596, 1569, 1463, 1372, 1227, 1118 cm −1. MS (CI)m/z(rel intensity) 497 (MH+, 86), 500 (15), 499 (99), 497 (86), 419 (28), 283 (18), 231 (22), 136 (17), 77 (46), 60 (13), 58 (18). HRMS (ESI) calcd for C23H27N2O3F2Br+H1 497.1252, found 497.1248. Anal. Calcd for C23H27BrF2N2O3+HCl+0.5H2O: C, 50.89; H, 5.38; N, 5.16; Found: C, 50.95; H, 5.37; N, 5.05.

Workup

  1. concentrationIt is concentrated in vacuo
  2. additiondiluted with ethyl acetate
  3. washwashed with 10% Na2CO3
  4. dry with materialThe solution is dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to a colorless oil
  7. dissolutionThis is dissolved in 3 mL of CH2Cl2
  8. concentrationAfter 2.5 h the mixture is concentrated
  9. washThe organic phase is washed with 1N KH2PO4, with brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated
  12. customchromatographed over silica gel
  13. washElution with 4% methanol (containing 1% of NH4OH) in CH2Cl2
  14. customaffords a sticky solid
  15. concentrationConcentration

Sources & evidence

ORD record
ord-90eeb298775345128979759822130ecc
Source dataset
uspto-grants-2010_01
Patent number
US07645780B2

Reaction notes

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