Methanol → HCID 69085923, compound

HRID 1396272Notes

Reaction equation

HRID 1396272 reaction equation
C([O:8][C@@H:9]1[C@@H:17]([C@@H:18]([O:21]CC2C=CC=CC=2)[CH2:19][F:20])[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([N:29]([CH3:31])[CH3:30])[S:14]2)[C@H:10]1[O:32]CC1C=CC=CC=1)C1C=CC=CC=1.B(Cl)(Cl)Cl.CO.[NH4+].[OH-]>ClCCl>[CH3:30][N:29]([CH3:31])[C:13]1[S:14][C@H:15]2[O:16][C@H:17]([C@H:18]([OH:21])[CH2:19][F:20])[C@@H:9]([OH:8])[C@H:10]([OH:32])[C@H:11]2[N:12]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 14923Ammonium HydroxideHCID 25135Boron TrichlorideHCID 69085414HCID 69085414, compound

Product 1

HCID 69085923HCID 69085923, compoundYield 23.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 104 (400 mg, 0.7 mmol) in dichloromethane (15 mL) was treated with BCl3 (7 mL, 7 mmol, 1M in dichloromethane) for 30 min at −60° 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 100% in 8 min Detector, 220 nm to afford (3aR,5S,6S,7R,7aR)-2-(dimethylamino)-5-((S)-2-fluoro-1-hydroxyethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as a white solid (46.3 mg, 23%), faster eluting isomer; (ES, m/z): [M+H]+ 281.0; III NMR (300 MHz, D2O) δ 6.17 (d, J=6.6 Hz, 1H), 4.29-4.69 (m, 2H), 3.95-4.15 (m, 3H), 3.68-3.72 (m, 1H), 3.54-3.58 (m, 1H), 2.88 (s, 3H), 2.87 (s, 3H); and (3aR,5S,6S,7R,7aR)-2-(dimethylamino)-5-((R)-2-fluoro-1-hydroxyethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as a white solid (64 mg, 31%), slower eluting isomer; (ES, m/z): [M+H]+ 281.0; 1H NMR (300 MHz, D2O) δ 6.17 (d, 6.3 Hz, 1H), 4.44-4.57 (m, 1H), 4.28-4.39 (m, 1H), 3.92-4.12 (m, 3H), 3.67-3.72 (m, 1H), 3.27-3.49 (m, 1H), 2.89 (s, 3H), 2.87 (s, 3H).

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-4e99b75af9ce4253bd78b932613bd67c
Source dataset
uspto-grants-2014_12
Patent number
US08901087B2

Reaction notes

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