Triethylamine → Ethyl 2-(tert-butoxycarbonylamino)-2-(hydroxymethyl)hex-5-enoate

HRID 579512Notes

Reaction equation

HRID 579512 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([C:17]([O:19][CH2:20][CH3:21])=[O:18])([CH2:13][CH2:14][CH:15]=[CH2:16])[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(OCC)=O.[BH4-].[Na+]>C1COCC1.O>[C:1]([O:5][C:6]([NH:8][C:9]([CH2:10][OH:11])([CH2:13][CH2:14][CH:15]=[CH2:16])[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 715799912-(Tert-butoxycarbonylamino)-2-(ethoxycarbonyl)hex-5-enoic acid

Product 1

HCID 71579992Ethyl 2-(tert-butoxycarbonylamino)-2-(hydroxymethyl)hex-5-enoateYield 78.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

A solution of the 2-(tert-butoxycarbonylamino)-2-(ethoxycarbonyl)hex-5-enoic acid (7.5 g, 24.9 mmol) and triethylamine (3.01 g, 29.9 mmol, 4.15 mL) in THF (10 mL) was cooled to −40° C. and treated with ethyl chloroformate (2.97 g, 27.4 mmol, 2.65 mL). After stirring for 30 minutes, the precipitate (triethylamine hydrochloride) was removed by filtration and the filtrate was collected and cooled to −40° C. A solution of sodiumborohydride (950 mg, 24.9 mmol) in water (10 mL) was added and the resulting solution was stirred for 30 minutes. After quenching the reaction mixture with 3 N hydrochloric acid (5 mL), the mixture was diluted with ethyl acetate (150 mL), washed with water (1×50 mL) and extracted with ethyl acetate (1×150 mL). The combined organic layers were concentrated, dried over MgSO4, filtered and purified using a combiflash system (80 g silica gel column, eluting with 10-50% ethyl acetate in heptanes) to give ethyl 2-(tert-butoxycarbonylamino)-2-(hydroxymethyl)hex-5-enoate (5.6 g, 78%). 1H NMR (CDCl3) δ 5.71-5.62 (m, 1H), 5.52 (bs, 1H), 4.96-4.87 (m, 2H), 4.20-4.12 (m, 2H) 4.07-4.03 (m, 2H), 3.73 (d, J=12.0 Hz, 1H), 2.22-1.62 (m, 4H), 1.37 (m, 9H), 1.22 (t, J=7.2 Hz, 3H).

Workup

  1. customthe precipitate (triethylamine hydrochloride) was removed by filtration
  2. customthe filtrate was collected
  3. stirringthe resulting solution was stirred for 30 minutes
  4. customAfter quenching the reaction mixture with 3 N hydrochloric acid (5 mL)
  5. additionthe mixture was diluted with ethyl acetate (150 mL)
  6. washwashed with water (1×50 mL)
  7. extractionextracted with ethyl acetate (1×150 mL)
  8. concentrationThe combined organic layers were concentrated
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. custompurified
  12. washa combiflash system (80 g silica gel column, eluting with 10-50% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-0439863d044c48dd858132146fde6697
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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