Sodium borohydride → tert-Butyl ((2S,4R)-1-azido-7-chloro-4-(hydroxymethyl)heptan-2-yl)carbamate

HRID 218438Notes

Reaction equation

HRID 218438 reaction equation
[N:1]([CH2:4][C@H:5]1[N:9]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:8](=[O:17])[C@H:7]([CH2:18][CH2:19][CH2:20][Cl:21])[CH2:6]1)=[N+:2]=[N-:3].[BH4-].[Na+]>CO>[N:1]([CH2:4][C@@H:5]([NH:9][C:10](=[O:11])[O:12][C:13]([CH3:15])([CH3:14])[CH3:16])[CH2:6][C@H:7]([CH2:8][OH:17])[CH2:18][CH2:19][CH2:20][Cl:21])=[N+:2]=[N-:3]

Participants

4

Reactant 2

HCID 4311764Sodium borohydride3×HCID 58011552(3R,5S)-tert-butyl 5-(azidomethyl)-3-(3-chloropropyl)-2-oxopyrrolidine-1-carboxylate

Product 1

HCID 58011485tert-Butyl ((2S,4R)-1-azido-7-chloro-4-(hydroxymethyl)heptan-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
27 °C

Procedure

The (3R,5S)-tert-butyl 5-(azidomethyl)-3-(3-chloropropyl)-2-oxopyrrolidine-1-carboxylate (10.11 g, 31.9 mmol, 10. equiv) was dissolved in 200 mL of MeOH. Solid NaBH4 was added in ˜1 g portions at a rate to maintain the reaction temperature at ˜27° C. Subsequent portions of NaBH4 were added only after the previous charge had completely dissolved. After the addition of ˜3 g of NaBH4 (˜80 mmol, 2.5 equiv) over a 3 h period, LC/MS analysis showed >95% conversion to the desired alcohol. The residual hydride reagent was quenched by cooling the mixture to 0° C. and carefully adding 1.0 M HCl until H2 evolution ceased. The methanol was removed in vacuo and the mixture diluted with ˜200 mL of EtOAc. The mixture was transferred to a separatory funnel and the layers separated. The aqueous layer was extracted with additional EtOAc and the combined organic layers washed with brine, dried over Na2SO4, filtered through a pad of silica and evaporated. This yielded ˜10 g of tert-butyl (2S,4R)-1-azido-7-chloro-4-(hydroxymethyl)heptan-2-ylcarbamate which possessed sufficient purity to employ in the subsequent step with no further purification.

Workup

  1. additionprevious charge
  2. dissolutionhad completely dissolved
  3. customThe residual hydride reagent was quenched
  4. temperatureby cooling the mixture to 0° C.
  5. additioncarefully adding 1.0 M HCl until H2 evolution
  6. customThe methanol was removed in vacuo
  7. additionthe mixture diluted with ˜200 mL of EtOAc
  8. customThe mixture was transferred to a separatory funnel
  9. customthe layers separated
  10. extractionThe aqueous layer was extracted with additional EtOAc
  11. washthe combined organic layers washed with brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered through a pad of silica
  14. customevaporated
  15. customto employ in the subsequent step with no further purification

Sources & evidence

ORD record
ord-510c363fa9f34af1987c6ffec1f551f9
Source dataset
uspto-grants-2012_06
Patent number
US08198453B2

Reaction notes

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