5-Tert-butoxycarbonylamino-3-(3,5-difluoro-4-nitro-benzyl)-4-oxo-tetrahydro-thiopyran-3-carboxylic acid allyl ester → HCID 57386307, compound

HRID 420302Notes

Reaction equation

HRID 420302 reaction equation
C(OC([C:7]1([CH2:22][C:23]2[CH:28]=[C:27]([F:29])[C:26]([N+:30]([O-:32])=[O:31])=[C:25]([F:33])[CH:24]=2)[C:12](=[O:13])[CH:11]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10][S:9][CH2:8]1)=O)C=C>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:18]([O:17][C:15](=[O:16])[NH:14][C@@H:11]1[C:12](=[O:13])[C@H:7]([CH2:22][C:23]2[CH:24]=[C:25]([F:33])[C:26]([N+:30]([O-:32])=[O:31])=[C:27]([F:29])[CH:28]=2)[CH2:8][S:9][CH2:10]1)([CH3:21])([CH3:19])[CH3:20]

Participants

4

Reactant 1

HCID 666495975-Tert-butoxycarbonylamino-3-(3,5-difluoro-4-nitro-benzyl)-4-oxo-tetrahydro-thiopyran-3-carboxylic acid allyl ester

Product 1

HCID 57386307HCID 57386307, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a degassed solution of 5-tert-butoxycarbonylamino-3-(3,5-difluoro-4-nitro-benzyl)-4-oxo-tetrahydro-thiopyran-3-carboxylic acid allyl ester (30.4 g, 62.4 mmol) in THF (300 mL) was added under argon 5,5-dimethyl-cyclohexane-1,3-dione (11.6 g, 81.2 mmol) and Pd(PPh3)4 (0.76 g, 0.62 mmol) and the reaction mixture was stirred for 3 h at 25° C. The reaction mixture was poured into aq. NaH2PO4 solution, concentrated and extracted with EtOAc. Combined organic extracts were washed with brine, dried over MgSO4, filtered and evaporated. The crystallized product containing the (3R*,5S*)-diastereoisomer was filtered off and dried. The mother liquor containing a larger amount of the (3S*,5S*)-diastereoisomer was dissolved in THF and equilibrated with a catalytic amount of DBU to the (3R*,5S*)-diastereoisomer for 16 h at 25° C. After removal of the THF the (3R*,5S*)-diastereoisomer was crystallized from Et2O-hexane to provide more of the title compound as white crystals: TLC (hexane-EtOAc 3:1) Rf=0.23; HPLC RtA=2.23 min; ESIMS [M+NH4]+=420; 1H NMR (400 MHz, CDCl3): δ 6.96 (d, 2H), 5.65 (d, 1H), 4.55 (m, 1H), 3.40 (m, 1H), 3.25 (dd, 1H), 3.14 (m, 1H), 2.86 (m, 1H), 2.6-2.75 (m, 3H), 1.44 (s, 9H).

Workup

  1. concentrationconcentrated
  2. extractionextracted with EtOAc
  3. washCombined organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. additionThe crystallized product containing the (3R*,5S*)-diastereoisomer
  8. filtrationwas filtered off
  9. customdried
  10. additionThe mother liquor containing a larger amount of the (3S*,5S*)-diastereoisomer
  11. dissolutionwas dissolved in THF
  12. customAfter removal of the THF the (3R*,5S*)-diastereoisomer
  13. customwas crystallized from Et2O-hexane

Sources & evidence

ORD record
ord-4ae25ecadf04445b94047a3f950e690a
Source dataset
uspto-grants-2012_01
Patent number
US08093406B2

Reaction notes

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