Hydrochloric Acid → Tert-butyl (3-hydroxy-1-phenylpropyl)carbamate

HRID 659128Notes

Reaction equation

HRID 659128 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:10][C:11](O)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(OC)=O.[BH4-].[Na+].Cl>O1CCCC1.C(N(CC)CC)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:10][CH2:11][OH:12])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 27568153-{[(Tert-butoxy)carbonyl]amino}-3-phenylpropanoic acid2×HCID 4311764Sodium borohydride

Product 1

HCID 21803951Tert-butyl (3-hydroxy-1-phenylpropyl)carbamateYield 36%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

To a 17.9 mmol suspension of 3-(tert-butoxycarbonylamino)-3-phenylpropanoic acid (Formula 10) in tetrahydrofuran (THF) at 0° C. was added 2.74 mL of triethyl amine and 1.52 mL of methyl chloroformate. The mixture was stirred at 0° C. for 15 minutes. Next, the white solid formed was filtered off and washed with 10 mL of THF. The filtrate was added drop-wise to 8.4 mL of 26.8 mmol sodium borohydride at 0° C. and stirred for 30 min. The mixture was then stirred at room temperature for 2 hr. Ten percent hydrochloric acid (HCl) was added until a pH of 2 was reached, and then was extracted using ethyl acetate. The resulting combined ethyl acetate layers were washed with sodium carbonate, water, brine, and concentrated. Column chromatography (50% ethyl acetate/hexane) gave 1.63 g (36%) of the title compound as a colorless oil. The aqueous phase was acidified with HCl and extracted with ethyl acetate to recover 2 g of 3-(tert-butoxycarbonylamino)-3-phenylpropanoic acid. 1H NMR (300 MHz, CDCl3) δ 1.45 (s, 9H), 1.62-1.63 (m, 1H), 1.79-1.87 (m, 1H), 3.68-3.74 (m, 2H), 5.23 (br, 1H), 5.32 (br, 1H), 7.26-7.38 (m, 5H).

Workup

  1. customNext, the white solid formed
  2. filtrationwas filtered off
  3. washwashed with 10 mL of THF
  4. stirringstirred for 30 min
  5. stirringThe mixture was then stirred at room temperature for 2 hr
  6. extractionwas extracted
  7. washwere washed with sodium carbonate, water, brine
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-5e00b26ae073460fb7bb503be90155f9
Source dataset
uspto-grants-2011_12
Patent number
US08080570B2

Reaction notes

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