Potassium bisulfate → [(3R*,4R*,5S*)-5-(3-Fluoro-4-nitro-benzyl)-4-hydroxy-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl ester

HRID 420266Notes

Reaction equation

HRID 420266 reaction equation
[B-].[B-].C1CCOCC1.C1CCOCC1.[Ca+2].[C:16]([O:20][C:21](=[O:41])[NH:22][C@@H:23]1[C:28](=[O:29])[C@H:27]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[C:33]([F:40])[CH:32]=2)[CH2:26][S:25][CH2:24]1)([CH3:19])([CH3:18])[CH3:17].OS([O-])(=O)=O.[K+]>C1COCC1>[C:16]([O:20][C:21](=[O:41])[NH:22][C@@H:23]1[C@H:28]([OH:29])[C@H:27]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[C:33]([F:40])[CH:32]=2)[CH2:26][S:25][CH2:24]1)([CH3:19])([CH3:17])[CH3:18]

Participants

5

Reactant 3

HCID 516920Potassium bisulfateHCID 57386559HCID 57386559, compoundHCID 90478304CID 90478304

Product 1

HCID 68553360[(3R*,4R*,5S*)-5-(3-Fluoro-4-nitro-benzyl)-4-hydroxy-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

To a solution of calcium borohydride bis-THF complex (1.14 g, 4.6 mmol) in anhydrous THF (100 mL) was added under argon a solution of [(3R*,5S*)-5-(3-fluoro-4-nitro-benzyl)-4-oxo-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl ester (1.77 g, 4.6 mmol) in THF (50 mL) at −70° C. The reaction mixture was slowly warmed to −40° C. and stirred for 1 h at −40° C. The reaction mixture was poured onto a cold aq. KHSO4 solution and the product was extracted with EtOAc. Combined extracts were washed with NaHCO3 solution and brine, dried over MgSO4 and evaporated. The mixture of diastereoisomers was separated by flash-chromatography on silica gel (toluene-EtOAc 6:1 to 3:1) to yield the undesired [(3R*,4S*,5S*)-diastereoisomer and the desired [(3R*,4R*,5S*)-diastereoisomer after crystallization from EtOH as a white crystalline solid: TLC (toluene-EtOAc 3:1) Rf=0.20; HPLC RtA=1.94 min; ESIMS [M+H-isobutylene]+=331; 1H NMR (600 MHz, DMSO-d6): δ 8.09 (t, 1H), 7.41 (d, 1H), 7.27 (d, 1H), 6.67 (d, 1H), 4.94 (d, 1H), 3.42 (m, 1H), 3.27 (dd, 1H), 2.91 (m, 1H), 2.55 (m, 2H), 2.39 (dd, 1H), 2.24 (m, 2H), 1.93 (m, 1H), 1.37 (s, 9H).

Workup

  1. extractionthe product was extracted with EtOAc
  2. washCombined extracts were washed with NaHCO3 solution and brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. additionThe mixture of diastereoisomers
  6. customwas separated by flash-chromatography on silica gel (toluene-EtOAc 6:1 to 3:1)
  7. customto yield the undesired [(3R*,4S*,5S*)-diastereoisomer
  8. customafter crystallization from EtOH as a white crystalline solid
  9. customHPLC RtA=1.94 min

Sources & evidence

ORD record
ord-1bcceaaef24f47afaa5ddee49970029c
Source dataset
uspto-grants-2012_01
Patent number
US08093406B2

Reaction notes

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