Methanol → HCID 69082878, compound

HRID 1396268Notes

Reaction equation

HRID 1396268 reaction equation
C([O:8][C@@H:9]1[C@@H:17]([C@@H:18]([O:22]CC2C=CC=CC=2)[CH:19]([F:21])[F:20])[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([N:30]([CH3:32])[CH3:31])[S:14]2)[C@H:10]1[O:33]CC1C=CC=CC=1)C1C=CC=CC=1.B(Cl)(Cl)Cl.CO.[NH4+].[OH-]>ClCCl>[F:21][CH:19]([F:20])[C@H:18]([C@H:17]1[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([N:30]([CH3:31])[CH3:32])[S:14]2)[C@@H:10]([OH:33])[C@@H:9]1[OH:8])[OH:22]

Participants

6

Reactant 4

HCID 887MethanolHCID 14923Ammonium HydroxideHCID 25135Boron TrichlorideHCID 69086109HCID 69086109, compound

Product 1

HCID 69082878HCID 69082878, compoundYield 5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 99 (600 mg, 1 mmol) in dichloromethane (20 mL) was treated with BCl3 (10 mL, 10 mmol, 1 M in dichloromethane) for 1 hour at −78° C., then quenched with methanol (20 mL). Volatiles were distilled out to give a residue, which was dissolved into methanol (5 mL) and neutralized with Con. NH4OH (2 ml, 26% aqueous solution). After concentration, the crude product was purified by a silica gel column, eluted with 10% methanol in dichloromethane to give a mixture of the two epimers; the two epimers were separated by Prep-HPLC with the following conditions: (Agilent Prep 1200 Detecl): Column, SunFire Prep C18; mobile phase, Water with 0.05% ammonia and CH3CN, 5% CH3CN up to 40% in 8 min; Detector, 220 nm) to afford (3aR,5S,6S,7R,7aR)-5-((S)-2,2-difluoro-1-hydroxyethyl)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as a light yellow solid (14.4 mg, 5%), faster eluting isomer; (ES, m/z) [M+H]+ 299.0, 1H NMR (300 MHz, D2O) δ 6.19 (d, J=6.6 Hz, 1H), 5.71-6.09 (m, 1H), 4.15 (t, J=6.0 Hz, 1H), 3.89-3.99 (m, 2H), 3.78-3.82 (m, 1H), 3.37 (t, J=8.7 Hz, 1H), 2.89 (s, 6H); and (3aR,5S,6S,7R,7aR)-5-((R)-2,2-difluoro-1-hydroxyethyl)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as a light yellow solid (53.9 mg, 17.4%), slower eluting isomer; (ES, m/z) [M+H]+ 299.0, 1H NMR (300 MHz, D2O) δ 6.20 (d, J=6.3 Hz, 1H), 5.62-6.00 (m, 1H), 4.07 (t, J=6.0 Hz, 1H), 3.87-3.96 (m, 2H), 3.72-3.77 (m, 1H), 3.62-3.65 (m, 1H), 2.88 (s, 6H).

Workup

  1. customquenched with methanol (20 mL)
  2. distillationVolatiles were distilled out
  3. customto give a residue, which
  4. concentrationAfter concentration
  5. customthe crude product was purified by a silica gel column
  6. washeluted with 10% methanol in dichloromethane
  7. customto give
  8. additiona mixture of the two epimers
  9. customthe two epimers were separated by Prep-HPLC with the following conditions

Sources & evidence

ORD record
ord-143843d54a974b7ba9523f21979350d3
Source dataset
uspto-grants-2014_12
Patent number
US08901087B2

Reaction notes

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