Methanol → HCID 69280774, compound

HRID 1396294Notes

Reaction equation

HRID 1396294 reaction equation
C([O:8][C@@H:9]1[C@@H:17]([CH:18]([OH:23])[C:19]([F:22])([F:21])[F:20])[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([NH:24]C(=O)OC(C)(C)C)[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>[NH2:24][C:13]1[S:14][C@H:15]2[O:16][C@H:17]([C@H:18]([OH:23])[C:19]([F:22])([F:21])[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 86701124HCID 86701124, compound

Product 1

HCID 69280774HCID 69280774, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 142 (1 g, 1.7 mmol) in dichloromethane (30 mL) was treated with BCl3 (17 mL, 17 mmol, 1M dichloromethane) at −78° C. for 4 hours. The reaction was quenched by addition of methanol (10 mL). Removal of volatiles gave a residue, which was dissolved into methanol (5 mL) and neutralized with concentrated NH4OH (2 mL). After concentrated under reduced pressure, the crude product was purified by a silica gel column, eluted with 5%-20% methanol in dichloromethane to give a mixture of the above two compounds. Separation by Prep-HPLC with the following conditions (Column, Sun fire prep. C18; mobile phase, water with 0.03% NH4OH and CH3CN (10% up to 45% in 10 min); Detector, UV 220 nm) gave (3aR,5S,6S,7R,7aR)-2-amino-5-[(1S)-2,2,2-trifluoro-1-hydroxyethyl]-3aH,5H,6H,7H,7aH-pyrano[3,2-d][1,3]thiazole-6,7-diol Example 164 as a light yellow solid (49 mg, 20%, faster eluting isomer); (ES, m/z): [M+H]+ 289.0; 1H NMR (400 MHz, D2O) δ 6.25 (d, J=6.8 Hz, 1H), 4.29-4.26 (m, 2H), 4.07 (t, J=4.0 Hz, 1H), 3.93 (dd, J=8.4, 3.2 Hz, 1H), 3.73 (dd, J=8.4, 4.8 Hz, 1H); and (3aR,5S,6S,7R,7aR)-2-amino-5-[(1R)-2,2,2-trifluoro-1-hydroxyethyl]-3aH,5H,6H,7H,7aH-pyrano[3,2-d][1,3]thiazole-6,7-diol as a light yellow solid (74 mg, 30%, slower eluting isomer); (ES, m/z): [M+H]+ 289.0; 1HNMR (400 MHz, D2O) δ 6.32 (d, J=6.4 Hz, 1H), 4.31 (q, J=7.6 Hz, 1H), 4.15 (t, J=6.0 Hz, 1H), 4.00 (t, J=5.0 Hz, 1H), 3.83-3.76 (m, 2H).

Workup

  1. customThe reaction was quenched by addition of methanol (10 mL)
  2. customRemoval of volatiles
  3. customgave a residue, which
  4. concentrationAfter concentrated under reduced pressure
  5. customthe crude product was purified by a silica gel column
  6. washeluted with 5%-20% methanol in dichloromethane
  7. customto give
  8. additiona mixture of the above two compounds
  9. customSeparation by Prep-HPLC with the following conditions (Column, Sun fire prep. C18; mobile phase, water with 0.03% NH4OH and CH3CN (10% up to 45% in 10 min); Detector, UV 220 nm)

Sources & evidence

ORD record
ord-33fde3c9e8574daaafe602832ee0b25b
Source dataset
uspto-grants-2014_12
Patent number
US08901087B2

Reaction notes

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