Hydrochloric Acid → HCID 131729381, compound

HRID 420306Notes

Reaction equation

HRID 420306 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([CH:36]=[CH:37][CH:38]=1)[CH2:8][NH:9][C@@H:10]1[C@@H:15]([OH:16])[C@H:14]([CH2:17][C:18]2[CH:23]=[C:22]([O:24][CH2:25][C:26](F)(F)F)[C:21]([N+:30]([O-])=O)=[C:20]([F:33])[CH:19]=2)[CH2:13][S:12](=[O:35])(=[O:34])[CH2:11]1)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].[ClH:41].[CH3:42][OH:43]>CCOCC>[ClH:41].[ClH:41].[NH2:30][C:21]1[C:22]([O:24][CH2:25][CH2:26][O:43][CH3:42])=[CH:23][C:18]([CH2:17][C@H:14]2[C@H:15]([OH:16])[C@@H:10]([NH:9][CH2:8][C:7]3[CH:36]=[CH:37][CH:38]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:6]=3)[CH2:11][S:12](=[O:35])(=[O:34])[CH2:13]2)=[CH:19][C:20]=1[F:33]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 4311764Sodium borohydrideHCID 131729382HCID 131729382, compound

Product 1

HCID 131729381HCID 131729381, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
2.5 °C

Procedure

To a solution of (3R,4S,5S)-3-(3-tert-butyl-benzylamino)-5-[3-fluoro-4-nitro-5-(2,2,2-trifluoro-ethoxy)-benzyl]-1,1-dioxo-hexahydro-1lambda*6*-thiopyran-4-ol (0.082 g, 0.166 mol) in MeOH (5 mL) was added NiCl2-6H2O (0.038 g, 0.155 mmol) and at 0° C. NaBH4 (0.024 g, 0.62 mmol) in two portions. After stirring for 1 h at 0-5° C. the reaction was quenched by addition of 1N aq. HCl. The reaction mixture was stirred for 0.5 h at 25° C. and extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. Chromatographic purification (Combi-Flash, 4 g, hexane-THF 90:10 to 10:90 containing 0.5% NEt3) provided a pure yellow oil which was converted into the hydrochloride salt with 1N HCl in Et2O to yield the title compound as a white amorphous solid: TLC (hexane-THF 2:3) Rf=0.22; HPLC RtA=1.56 min; ESIMS [M+NH4]+=509; 1H NMR (600 MHz, DMSO-d6): δ 9.89 (s, 1H), 9.08 (s, 1H), 7.67 (s, 1H), 7.43 (m, 1H), 7.38 (m, 2H), 6.62 (m, 2H), 6.18 (s, 1H), 4.24 (m, 2H), 4.14 (m, 2H), 3.82 (m, 1H), 3.3-3.7 (m, 5H), 3.29 (s, 3H), 3.24 (m, 2H), 3.03 (dd, 1H), 2.77 (m, 1H), 2.40 (dd, 1H), 2.04 (m, 1H), 1.35 (d, 9H).

Workup

  1. customat 0° C
  2. customwas quenched by addition of 1N aq. HCl
  3. stirringThe reaction mixture was stirred for 0.5 h at 25° C.
  4. extractionextracted with EtOAc
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customChromatographic purification (Combi-Flash, 4 g, hexane-THF 90:10 to 10:90 containing 0.5% NEt3)
  10. customprovided a pure yellow oil which

Sources & evidence

ORD record
ord-11dff48c1e8b41749fd0c68ca741e5a5
Source dataset
uspto-grants-2012_01
Patent number
US08093406B2

Reaction notes

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