Hydrochloric Acid → Ethyl 2-(benzyloxycarbonylamino)-2-(hydroxymethyl)hex-5-enoate

HRID 579503Notes

Reaction equation

HRID 579503 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]([C:20]([O:22][CH2:23][CH3:24])=[O:21])([CH2:16][CH2:17][CH:18]=[CH2:19])[C:13](O)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OCC)=O.[BH4-].[Na+].Cl>O1CCCC1.O.C(OCC)(=O)C>[CH2:1]([O:8][C:9]([NH:11][C:12]([CH2:13][OH:14])([CH2:16][CH2:17][CH:18]=[CH2:19])[C:20]([O:22][CH2:23][CH3:24])=[O:21])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 668331922-(Benzyloxycarbonylamino)-2-(ethoxycarbonyl)hex-5-enoic acid

Product 1

HCID 66833560Ethyl 2-(benzyloxycarbonylamino)-2-(hydroxymethyl)hex-5-enoateYield 48%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-(benzyloxycarbonylamino)-2-(ethoxycarbonyl)hex-5-enoic acid (1.54 g, 4.6 mmol) and triethylamine (557 mg, 5.52 mmol, 0.76 mL) in tetrahydrofuran (10 mL) was cooled to −30° C. and treated with ethyl chloroformate (522 mg, 4.82 mmol, 0.46 mL) and stirred for 30 minutes. A solution of sodium borohydride (175 mg, 4.6 mmol) in water (2 mL) was added and the mixture was stirred for 30 minutes. Once the reaction was complete, 3 N hydrochloric acid (1 mL) was added and the mixture was diluted with ethyl acetate (50 mL), washed with water (1×50 mL) and extracted with ethyl acetate (1×50 mL). The combined organic layers were concentrated and purified using a combiflash system (2×12 g silica gel column, eluting with 10-50% ethyl acetate in heptanes) to give ethyl 2-(benzyloxycarbonylamino)-2-(hydroxymethyl)hex-5-enoate (700 mg, 48%). 1H NMR (CDCl3) δ 7.29 (m, 5H), 5.82 (bs, 1H), 5.68-5.62 (m, 1H), 5.03 (s, 1H), 4.94-4.86 (m, 2H), 4.17 (m, 2H) 3.76 (dd, J=11.4 Hz, 1H), 1.97 (m, 2H), 1.77 (m, 2H), 1.21 (t, J=7.2 Hz, 3H). MS found for C17H23NO5 m/z [322 (M+1)].

Workup

  1. stirringthe mixture was stirred for 30 minutes
  2. washwashed with water (1×50 mL)
  3. extractionextracted with ethyl acetate (1×50 mL)
  4. concentrationThe combined organic layers were concentrated
  5. custompurified
  6. washa combiflash system (2×12 g silica gel column, eluting with 10-50% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-f988b6edff0040f9813d8b46741866ff
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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