Boron tribromide → (1R,10R,11S,16S)-5-hydroxy-N,1,11,15,15-pentamethyl-8-thiatetracyclo-[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carboxamide

HRID 422170Notes

Reaction equation

HRID 422170 reaction equation
C[O:2][C:3]1[CH:20]=[C:19]2[C:6]([C@@:7]3([CH3:24])[C@H:16]([CH2:17][S:18]2)[C@:15]2([CH3:21])[C@H:10]([C:11]([CH3:23])([CH3:22])[CH2:12][CH2:13][CH2:14]2)[CH2:9][CH2:8]3)=[C:5]([C:25]([NH:27][CH3:28])=[O:26])[CH:4]=1.B(Br)(Br)Br>C(Cl)Cl>[OH:2][C:3]1[CH:20]=[C:19]2[C:6]([C@@:7]3([CH3:24])[C@H:16]([CH2:17][S:18]2)[C@:15]2([CH3:21])[C@H:10]([C:11]([CH3:22])([CH3:23])[CH2:12][CH2:13][CH2:14]2)[CH2:9][CH2:8]3)=[C:5]([C:25]([NH:27][CH3:28])=[O:26])[CH:4]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 58294801(1R,10R,11S,16S)-5-methoxy-N,1,11,15,15-pentamethyl-8-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carboxamide

Product 1

HCID 58294828(1R,10R,11S,16S)-5-hydroxy-N,1,11,15,15-pentamethyl-8-thiatetracyclo-[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carboxamideYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (1R,10R,11S,16S)-5-methoxy-N,1,11,15,15-pentamethyl-8-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carboxamide (75) (0.17 g, 0.42 mmol) in anhydrous CH2Cl2 (5.0 mL) was cooled with an ice bath under N2. To the mixture BBr3 (1 M in CH2Cl2, 1.6 mL, 1.6 mmol) was added dropwise. The mixture was stirred at 0° C. for 2.5 h then at room temperature for 3.25 h. The solution was cooled to 0° C. and quenched with anhydrous MeOH. The solution was evaporated and the residue co-evaporated with anhydrous MeOH. The solid was suspended in EtOAc and washed with 0.09 M HCl (11 mL). The mixture was taken to pH=7.5 using sodium bicarbonate. The organic layer was separated was concentrated to dryness. The crude material was triturated with MeOH then filtered and washed with MeOH to yield (1R,10R,11S,16S)-5-hydroxy-N,1,11,15,15-pentamethyl-8-thiatetracyclo-[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carboxamide (76) (0.09 g, 57%) as a white solid. 1H NMR (DMSO-d6): δ 9.37 (s, 1H), 8.10 (m, 1H), 6.36 (d, 1H), 6.18 (d, 1H), 2.94 (dd, 1H), 2.80 (d, 1H), 2.65 (d, 3H), 1.81 (d, 1H), 1.62-1.26 (m, 12H), 1.09 (ddd, 1H), 0.87-0.81 (m, 7H), 0.78 (s, 3H). MS m/z 388 (C23H33NO2S+H+).

Workup

  1. waitat room temperature for 3.25 h
  2. temperatureThe solution was cooled to 0° C.
  3. customquenched with anhydrous MeOH
  4. customThe solution was evaporated
  5. washwashed with 0.09 M HCl (11 mL)
  6. customThe organic layer was separated
  7. concentrationwas concentrated to dryness
  8. customThe crude material was triturated with MeOH
  9. filtrationthen filtered
  10. washwashed with MeOH

Sources & evidence

ORD record
ord-5ca408624d354c9ca34163852ee39c63
Source dataset
uspto-grants-2012_01
Patent number
US08101605B2

Reaction notes

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