Hydrochloric Acid → HCID 23582534, compound

HRID 1874170Notes

Reaction equation

HRID 1874170 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@:15]([NH:30][C:31](=[O:40])[NH:32][C:33]2([C:36](OC)=[O:37])[CH2:35][CH2:34]2)([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:5]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:7]=1.[Li+].[BH4-].Cl>C1COCC1.CCOCC>[F:1][C:2]1[CH:3]=[C:4]([C@:15]([NH:30][C:31]([NH:32][C:33]2([CH2:36][OH:37])[CH2:35][CH2:34]2)=[O:40])([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:5]=[C:6]([O:8][C:9]([F:13])([F:14])[CH:10]([F:11])[F:12])[CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4148881Lithium borohydrideHCID 59459202HCID 59459202, compound

Product 1

HCID 23582534HCID 23582534, compoundYield 84.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (R)-methyl 1-(3-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)ureido)-cyclopropanecarboxylate (112 mg, 0.2 mmol), prepared by the method described in Procedure 30, in THF (0.2 mL) was added LiBH4 (0.2 mL, 2 M in THF, 0.4 mmol) at room temperature. The reaction mixture was stirred for 14 h, then cooled to 0° C. and 1 N HCl was added. The reaction mixture was diluted with ether. The organic layer was washed with H2O and sat. NaCl, dried over MgSO4, filtered and concentrated to give a colorless oil. The resulting oil was purified by ISCO chromatography (4 g column, eluting with 0-100% hexane/EtOAc over 16 min) to yield (R)-1-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-(1-(hydroxymethyl)cyclopropyl)urea (Example 241) as a white foam (91 mg, 84% yield). LCMS: RT=2.97 min [M+H] 539.2 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% CH3CN/H2O over 4 minutes containing 0.1% NH4OAc; 4 mL/min, monitoring at 220 nm); 1H NMR (400 MHz, CDCl3) ppm 0.61-0.81 (m, 4H), 2.50 (brs, 1H), 3.31-3.50 (m, 2H), 3.84 (qt, J=12 Hz, 2H), 4.93 (s, 1H), 5.84 (t, J=53 Hz, 1H), 6.53-7.05 (m, 8H), 7.05-7.24 (m, 5H).

Workup

  1. washThe organic layer was washed with H2O and sat. NaCl
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a colorless oil
  6. customThe resulting oil was purified by ISCO chromatography (4 g column, eluting with 0-100% hexane/EtOAc over 16 min)

Sources & evidence

ORD record
ord-e202d5d2faf14db7845aca10cb520fff
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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