Acetyl chloride → (2R)-2-(t-butoxycarbonylamino)-2-(4-(2-methylpentyloxy)phenyl)ethyl acetate

HRID 1874618Notes

Reaction equation

HRID 1874618 reaction equation
[OH:1][CH2:2][C@H:3]([NH:17][C:18](=[O:20])[O-:19])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH:12]([CH3:16])[CH2:13][CH2:14][CH3:15])=[CH:6][CH:5]=1.[CH2:21](N(CC)CC)C.[C:28](Cl)(=[O:30])[CH3:29].O1[CH2:36][CH2:35][CH2:34]C1>CN(C1C=CN=CC=1)C>[C:28]([O:1][CH2:2][C@H:3]([NH:17][C:18]([O:19][C:35]([CH3:34])([CH3:36])[CH3:21])=[O:20])[C:4]1[CH:5]=[CH:6][C:7]([O:10][CH2:11][CH:12]([CH3:16])[CH2:13][CH2:14][CH3:15])=[CH:8][CH:9]=1)(=[O:30])[CH3:29]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 86658394(1R)-2-hydroxy-1-(4-(2-methylpentyloxy)phenyl)ethylcarbamate

Product 1

HCID 67086154(2R)-2-(t-butoxycarbonylamino)-2-(4-(2-methylpentyloxy)phenyl)ethyl acetateYield 98%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

To a solution of (1R)-2-hydroxy-1-(4-(2-methylpentyloxy)phenyl)ethylcarbamate (5.00 g, 14.82 mmol) and triethylamine (10.33 mL, 74.1 mmol) in tetrahydrofuran (50 mL) at 0° C. was added DMAP (1.99 g, 16.30 mmol). Acetyl chloride (4.21 mL, 59.3 mmol) was then added slowly via syringe. After the addition was complete, the cooling bath was removed and the mixture was stirred at room temperature under N2 for 2 h. The reaction mixture was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (50 mL). The aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (15%→25% ethyl acetate in hexanes) to afford (2R)-2-(tert-butoxycarbonylamino)-2-(4-(2-methylpentyloxy)phenyl)ethyl acetate (5.50 g, 98% yield) as a colorless amorphous solid: 1H NMR (400 MHz, DMSO-d6) δ 7.44 (d, J=9.1 Hz, 1H), 7.23 (d, J=8.8 Hz, 2H), 6.88 (d, J=8.6 Hz, 2H), 4.67-4.78 (m, 1H), 4.10 (dd, J=10.8, 5.3 Hz, 1H), 3.98 (dd, J=10.6, 9.1 Hz, 1H), 3.80 (dd, J=9.6, 6.0 Hz, 1H), 3.71 (dd, J=9.3, 6.8 Hz, 1H), 1.97 (s, 3H), 1.86 (dq, J=12.8, 6.5 Hz, 1H), 1.37 (s, 9 H), 1.22-1.47 (m, 3H), 1.11-1.22 (m, 1H), 0.96 (d, J=6.8 Hz, 3H), 0.88 (t, J=7.2 Hz, 3H); LRMS (ESI) m/e 380.3 [(M+H)+, calcd for C21H34NO5 380.3].

Workup

  1. additionAfter the addition
  2. customthe cooling bath was removed
  3. customThe reaction mixture was transferred to a separatory funnel
  4. additioncontaining saturated aqueous NaHCO3 solution (50 mL)
  5. extractionThe aqueous layer was extracted with ethyl acetate (3×100 mL)
  6. washThe combined organic layers were washed with brine (50 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography on silica gel (15%→25% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-7b0ba9d2d7cf461298cb70e6ad3414e1
Source dataset
uspto-grants-2012_11
Patent number
US08304577B2

Reaction notes

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